首页 > 最新文献

Biometals最新文献

英文 中文
Can iron chelators ameliorate viral infections? 铁螯合剂能改善病毒感染吗?
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-29 DOI: 10.1007/s10534-023-00558-x
Tatiana Araujo Pereira, Breno Pannia Espósito

The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals.

铁的氧化还原活性对细胞功能来说是一把双刃剑,取决于金属的浓度和位置,它是必需的还是有害的。铁稳态失调与包括病毒感染在内的几种临床状况有关。临床研究以及计算机、体外和体内模型表明,几种病毒对铁水平有直接影响。铁螯合作为一种抑制感染和/或病毒复制的替代疗法得到了支持,其基本原理是铁是一些病毒蛋白质和基因合成所必需的。此外,铁水平异常会影响信号免疫反应。然而,其他研究报告了病毒感染对铁稳态的不同影响,这取决于病毒的类别和基因型,因此很难预测铁螯合是否有任何好处。本文综述了铁稳态与病毒感染的非特异性免疫反应之间的关系,以及它与炎症过程的进展或抑制的相关性,以阐明铁螯合剂作为抗病毒药物有效使用的情况。
{"title":"Can iron chelators ameliorate viral infections?","authors":"Tatiana Araujo Pereira,&nbsp;Breno Pannia Espósito","doi":"10.1007/s10534-023-00558-x","DOIUrl":"10.1007/s10534-023-00558-x","url":null,"abstract":"<div><p>The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"289 - 304"},"PeriodicalIF":4.1,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138450597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term Cu exposure alters CYP450s activity and induces jejunum injury and apoptosis in broilers 长期铜暴露可改变肉鸡空肠cyp450活性,诱导空肠损伤和细胞凋亡。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-22 DOI: 10.1007/s10534-023-00559-w
Lei Li, Gaolong Zhong, Yuanxu Li, Tingyu Li, Yihui Huo, Feiyang Ma, Ying Li, Hui Zhang, Jiaqiang Pan, Lianmei Hu, Jianzhao Liao, Zhaoxin Tang

Copper (Cu) is an essential trace element that plays a crucial role in numerous physiopathological processes related to human and animal health. In the poultry industry, Cu is used to promote growth as a feed supplement, but excessive use can lead to toxicity on animals. Cytochrome P450 enzymes (CYP450s) are a superfamily of proteins that require heme as a cofactor and are essential for the metabolism of xenobiotic compounds. The purpose of this study was to explore the influence of exposure to Cu on CYP450s activity and apoptosis in the jejunum of broilers. Hence, we first simulated the Cu exposure model by feeding chickens diets containing different amounts of Cu. In the present study, histopathological observations have revealed morphological damage to the jejunum. The expression levels of genes and proteins of intestinal barrier markers were prominently downregulated. While the mRNA expression level of the gene associated with CYP450s was significantly increased. Additionally, apoptosis-related genes and proteins (Bak1, Bax, Caspase-9, Caspase-3, and CytC) were also significantly augmented by excessive Cu, while simultaneously decreasing the expression of Bcl-2. It can be concluded that long-term Cu exposure affects CYP450s activity, disrupts intestinal barrier function, and causes apoptosis in broilers that ultimately leads to jejunum damage.

Graphical Abstract

铜(Cu)是一种必需的微量元素,在与人类和动物健康有关的许多生理病理过程中起着至关重要的作用。在家禽业中,铜被用作饲料补充剂来促进生长,但过量使用会导致动物中毒。细胞色素P450酶(cyp450)是一个需要血红素作为辅助因子的蛋白质超家族,对异种化合物的代谢至关重要。本研究旨在探讨铜暴露对肉鸡空肠cyp450活性和细胞凋亡的影响。因此,我们首先通过饲喂含有不同量铜的鸡饲料来模拟铜暴露模型。在本研究中,组织病理学观察显示空肠的形态学损伤。肠道屏障标志物的基因和蛋白表达水平显著下调。而cyp450相关基因mRNA表达量显著升高。此外,过量Cu也显著增加了凋亡相关基因和蛋白(Bak1、Bax、Caspase-9、Caspase-3、CytC),同时降低了Bcl-2的表达。由此可见,长期铜暴露可影响肉仔鸡体内cyp450活性,破坏肠道屏障功能,导致细胞凋亡,最终导致空肠损伤。
{"title":"Long-term Cu exposure alters CYP450s activity and induces jejunum injury and apoptosis in broilers","authors":"Lei Li,&nbsp;Gaolong Zhong,&nbsp;Yuanxu Li,&nbsp;Tingyu Li,&nbsp;Yihui Huo,&nbsp;Feiyang Ma,&nbsp;Ying Li,&nbsp;Hui Zhang,&nbsp;Jiaqiang Pan,&nbsp;Lianmei Hu,&nbsp;Jianzhao Liao,&nbsp;Zhaoxin Tang","doi":"10.1007/s10534-023-00559-w","DOIUrl":"10.1007/s10534-023-00559-w","url":null,"abstract":"<div><p>Copper (Cu) is an essential trace element that plays a crucial role in numerous physiopathological processes related to human and animal health. In the poultry industry, Cu is used to promote growth as a feed supplement, but excessive use can lead to toxicity on animals. Cytochrome P450 enzymes (CYP450s) are a superfamily of proteins that require heme as a cofactor and are essential for the metabolism of xenobiotic compounds. The purpose of this study was to explore the influence of exposure to Cu on CYP450s activity and apoptosis in the jejunum of broilers. Hence, we first simulated the Cu exposure model by feeding chickens diets containing different amounts of Cu. In the present study, histopathological observations have revealed morphological damage to the jejunum. The expression levels of genes and proteins of intestinal barrier markers were prominently downregulated. While the mRNA expression level of the gene associated with CYP450s was significantly increased. Additionally, apoptosis-related genes and proteins (Bak1, Bax, Caspase-9, Caspase-3, and CytC) were also significantly augmented by excessive Cu, while simultaneously decreasing the expression of Bcl-2. It can be concluded that long-term Cu exposure affects CYP450s activity, disrupts intestinal barrier function, and causes apoptosis in broilers that ultimately leads to jejunum damage.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"421 - 432"},"PeriodicalIF":4.1,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reductions in plasma and urine mercury concentrations following N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI) therapy: a post hoc analysis of data from a randomized human clinical trial N,N'bis-(2-巯基乙基)异眼胺(NBMI)治疗后血浆和尿汞浓度的降低:一项随机人体临床试验数据的事后分析
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-21 DOI: 10.1007/s10534-023-00560-3
David A. Geier, Mark R. Geier

Environmental mercury exposure possesses a significant risk to many human populations. At present there are no effective treatments for acute mercury toxicity. A new compound, N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI), a lipophilic chelating agent was created to tightly/irreversibly bind mercury. A post hoc dose-dependent analysis of NBMI therapy was undertaken on data from a randomized controlled NBMI human treatment trial on 36 Ecuadorian gold miners with elevated urinary mercury concentrations. Study subjects were randomly assigned to receive 100 milligram (mg) NBMI/day, 300 mg NBMI/day, or placebo for 14 days. For each study subject daily mg NBMI dose/Kilogram (Kg) bodyweight were determined and plasma and urine mercury concentrations (micrograms (µg)/Liter (L)) on study day 1 (pre-NBMI treatment), 15 (after 14 days of NBMI treatment) and 45 (30 days after NBMI treatment) were correlated with NBMI dosing using the linear regression statistic in SAS. Regression revealed significant inverse correlations between increasing per mg NBMI/Kg bodyweight/day and reduced concentrations of urinary and plasma mercury on study day 15 (reduced by in urine = 18–20 µg/L and plasma = 2 µg/L) and study day 30 (reduced by in urine = 15–20 µg/L and plasma = 4 µg/L) and significant correlations between reductions in mercury concentrations in urine and plasma. Significant 30% reductions in urinary mercury concentrations per mg NBMI/Kg bodyweight/day administered for 14 days were observed. This study supports the dose-dependent ability of NBMI therapy to significantly reduce mercury concentrations, particularly in the urine, in an acutely mercury exposed human population. NBMI therapy should be evaluated in other mercury exposed populations.

环境汞暴露对许多人群具有重大风险。目前还没有有效的治疗急性汞中毒的方法。制备了一种新的亲脂螯合剂N,N'bis-(2-巯基乙基)异眼苯二胺(NBMI),以紧密/不可逆地结合汞。对36名尿汞浓度升高的厄瓜多尔金矿工人进行的随机对照NBMI人体治疗试验数据进行了NBMI治疗的事后剂量依赖性分析。研究对象被随机分配接受100毫克(mg) NBMI/天,300毫克NBMI/天,或安慰剂14天。对每个研究对象每日mg NBMI剂量/ Kg体重进行测定,并在研究第1天(NBMI治疗前)、第15天(NBMI治疗后14天)和第45天(NBMI治疗后30天)的血浆和尿汞浓度(微克(µg)/升(L))与NBMI剂量进行SAS线性回归统计。回归显示,在研究第15天(尿中汞含量降低18-20µg/L,血浆汞含量降低2µg/L)和研究第30天(尿中汞含量降低15-20µg/L,血浆汞含量降低4µg/L),每mg NBMI/Kg体重/天的升高与尿液和血浆汞浓度降低之间存在显著的负相关,尿液和血浆汞浓度降低之间存在显著的相关。观察到连续14天每mg NBMI/Kg体重/天尿汞浓度显著降低30%。本研究支持NBMI治疗显著降低汞浓度,特别是急性汞暴露人群尿液中的汞浓度的剂量依赖性能力。在其他汞暴露人群中,应评估非bmi疗法。
{"title":"Reductions in plasma and urine mercury concentrations following N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI) therapy: a post hoc analysis of data from a randomized human clinical trial","authors":"David A. Geier,&nbsp;Mark R. Geier","doi":"10.1007/s10534-023-00560-3","DOIUrl":"10.1007/s10534-023-00560-3","url":null,"abstract":"<div><p>Environmental mercury exposure possesses a significant risk to many human populations. At present there are no effective treatments for acute mercury toxicity. A new compound, N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI), a lipophilic chelating agent was created to tightly/irreversibly bind mercury. A post hoc dose-dependent analysis of NBMI therapy was undertaken on data from a randomized controlled NBMI human treatment trial on 36 Ecuadorian gold miners with elevated urinary mercury concentrations. Study subjects were randomly assigned to receive 100 milligram (mg) NBMI/day, 300 mg NBMI/day, or placebo for 14 days. For each study subject daily mg NBMI dose/Kilogram (Kg) bodyweight were determined and plasma and urine mercury concentrations (micrograms (µg)/Liter (L)) on study day 1 (pre-NBMI treatment), 15 (after 14 days of NBMI treatment) and 45 (30 days after NBMI treatment) were correlated with NBMI dosing using the linear regression statistic in SAS. Regression revealed significant inverse correlations between increasing per mg NBMI/Kg bodyweight/day and reduced concentrations of urinary and plasma mercury on study day 15 (reduced by in urine = 18–20 µg/L and plasma = 2 µg/L) and study day 30 (reduced by in urine = 15–20 µg/L and plasma = 4 µg/L) and significant correlations between reductions in mercury concentrations in urine and plasma. Significant 30% reductions in urinary mercury concentrations per mg NBMI/Kg bodyweight/day administered for 14 days were observed. This study supports the dose-dependent ability of NBMI therapy to significantly reduce mercury concentrations, particularly in the urine, in an acutely mercury exposed human population. NBMI therapy should be evaluated in other mercury exposed populations.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"433 - 445"},"PeriodicalIF":4.1,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cadmium and copper-induced metabolic and proteomic changes in the root tip during early maize growth 镉和铜诱导玉米生长早期根尖代谢和蛋白质组学变化
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-21 DOI: 10.1007/s10534-023-00557-y
Carolina Lucila Matayoshi, Odalis Maholi Jiménez Guaman, Marcos Leopoldo Esteso, Micaela Pavoni, Martín Arán, Liliana Beatriz Pena, Susana Mabel Gallego

In this study, the metabolic adjustments performed by maize (Zea mays L.) seminal roots exposed to 25 µM Cd2+ or 25 µM Cu2+ at pre-emergence are compared, focusing on the proteomic changes after metal exposure. Root width was increased, and root length was decreased after 72 h of metal treatment. Both metals induced H2O2 accumulation and lipid peroxidation in the root tip. These changes were accompanied by increases in lipoxygenase activity and 4-hydroxy-2-nonenal content. NMR spectroscopy revealed that the abundance of 38 water-soluble metabolites was significantly modified by Cd and Cu exposure; this set of metabolites comprised carboxylic acids, amino acids, carbohydrates, and unidentified phenolic compounds. Linoleic acid content significantly decreased in Cu-treated samples. The total amount of proteins detected in maize root apexes was 2,171. Gene ontology enrichment analysis of the differentially accumulated proteins was performed to detect pathways probably affected by metal additions. Both metals altered redox homeostasis, up-regulated oxylipins biosynthetic process, and shifted metabolism towards the oxidative pentose-phosphate in the root apexes. However, the methionine salvage pathway appears as a key metabolic module only under Cd stress. The integrative analysis carried out in this study suggests that most molecular features behind the reprogramming of maize root tips to cope with cadmium and copper toxicity are common, but some are not.

在本研究中,比较了玉米(Zea mays L.)种子根在萌发前暴露于25µM Cd2+或25µM Cu2+环境下的代谢调节,重点研究了金属暴露后蛋白质组学的变化。金属处理72h后,根宽增加,根长减少。两种金属均诱导根尖过氧化氢积累和脂质过氧化。这些变化伴随着脂肪加氧酶活性和4-羟基-2-壬烯醛含量的增加。核磁共振结果显示,Cd和Cu对38种水溶性代谢物的丰度有显著影响;这组代谢物包括羧酸、氨基酸、碳水化合物和未识别的酚类化合物。铜处理后的样品中亚油酸含量显著降低。在玉米根尖检测到的蛋白质总量为2171个。对差异积累蛋白进行基因本体富集分析,以检测可能受金属添加影响的途径。这两种金属都改变了氧化还原稳态,上调了氧脂素的生物合成过程,并将代谢转向了根尖的氧化戊糖-磷酸。然而,蛋氨酸回收途径仅在镉胁迫下作为一个关键的代谢模块出现。本研究进行的综合分析表明,玉米根尖重编程以应对镉和铜毒性的大多数分子特征是共同的,但有些不是。
{"title":"Cadmium and copper-induced metabolic and proteomic changes in the root tip during early maize growth","authors":"Carolina Lucila Matayoshi,&nbsp;Odalis Maholi Jiménez Guaman,&nbsp;Marcos Leopoldo Esteso,&nbsp;Micaela Pavoni,&nbsp;Martín Arán,&nbsp;Liliana Beatriz Pena,&nbsp;Susana Mabel Gallego","doi":"10.1007/s10534-023-00557-y","DOIUrl":"10.1007/s10534-023-00557-y","url":null,"abstract":"<div><p>In this study, the metabolic adjustments performed by maize (<i>Zea mays</i> L.) seminal roots exposed to 25 µM Cd<sup>2+</sup> or 25 µM Cu<sup>2+</sup> at pre-emergence are compared, focusing on the proteomic changes after metal exposure. Root width was increased, and root length was decreased after 72 h of metal treatment. Both metals induced H<sub>2</sub>O<sub>2</sub> accumulation and lipid peroxidation in the root tip. These changes were accompanied by increases in lipoxygenase activity and 4-hydroxy-2-nonenal content. NMR spectroscopy revealed that the abundance of 38 water-soluble metabolites was significantly modified by Cd and Cu exposure; this set of metabolites comprised carboxylic acids, amino acids, carbohydrates, and unidentified phenolic compounds. Linoleic acid content significantly decreased in Cu-treated samples. The total amount of proteins detected in maize root apexes was 2,171. Gene ontology enrichment analysis of the differentially accumulated proteins was performed to detect pathways probably affected by metal additions. Both metals altered redox homeostasis, up-regulated oxylipins biosynthetic process, and shifted metabolism towards the oxidative pentose-phosphate in the root apexes. However, the methionine salvage pathway appears as a key metabolic module only under Cd stress. The integrative analysis carried out in this study suggests that most molecular features behind the reprogramming of maize root tips to cope with cadmium and copper toxicity are common, but some are not.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"405 - 419"},"PeriodicalIF":4.1,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic insights into the adaptation of Acinetobacter johnsonii RB2-047 to the heavy metal-contaminated subsurface mine environment 约氏不动杆菌RB2-047对重金属污染地下矿山环境适应性的基因组研究
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-16 DOI: 10.1007/s10534-023-00555-0
Ivana Timková, Lenka Maliničová, Lea Nosáľová, Mariana Kolesárová, Zuzana Lorková, Nikola Petrová, Peter Pristaš, Jana Kisková

The subsurface mine environments characterized by high levels of toxic metals and low nutrient availability represent an extreme threat to bacterial persistence. In recent study, the genomic analysis of the Acinetobacter johnsonii strain RB2-047 isolated from the Rozália Gold Mine in Slovakia was performed. As expected, the studied isolate showed a high level of heavy metal tolerance (minimum inhibitory concentrations were 500 mg/L for copper and nickel, 1,500 mg/L for lead, and 250 mg/L for zinc). The RB2-047 strain also showed noticeable resistance to several antibiotics (ampicillin, kanamycin, chloramphenicol, tetracycline and ciprofloxacin). The genomic composition analysis demonstrated a low number of antibiotic and metal resistance coding genes, but a high occurrence of efflux transporter genes located on the bacterial chromosome. The experimental inhibition of efflux pumps resulted in decreased tolerance to Zn and Ni (but not to Cu and Pb) and to all antibiotics tested. In addition, the H33342 dye-accumulation assay confirmed the high efflux activity in the RB2-047 isolate. These findings showed the important role of efflux pumps in the adaptation of Acinetobacter johsonii strain RB2-047 to metal polluted mine environment as well as in development of multi-antibiotic resistance.

矿井地下环境的特点是高水平的有毒金属和低营养物质的可用性对细菌的持久性构成极端威胁。在最近的研究中,对从斯洛伐克Rozália金矿分离的约氏不动杆菌RB2-047株进行了基因组分析。正如预期的那样,所研究的分离物显示出高水平的重金属耐受性(对铜和镍的最低抑制浓度为500 mg/L,对铅的最低抑制浓度为1500 mg/L,对锌的最低抑制浓度为250 mg/L)。RB2-047菌株对多种抗生素(氨苄西林、卡那霉素、氯霉素、四环素和环丙沙星)也表现出明显的耐药性。基因组组成分析表明,抗生素和金属抗性编码基因数量较少,但位于细菌染色体上的外排转运基因发生率高。外排泵的实验抑制导致对Zn和Ni(但对Cu和Pb没有)和所有抗生素的耐受性降低。此外,H33342染料积累实验证实了RB2-047分离物的高外排活性。这些结果表明,外排泵在约翰氏不动杆菌RB2-047对金属污染矿山环境的适应以及多种抗生素耐药性的形成中发挥了重要作用。
{"title":"Genomic insights into the adaptation of Acinetobacter johnsonii RB2-047 to the heavy metal-contaminated subsurface mine environment","authors":"Ivana Timková,&nbsp;Lenka Maliničová,&nbsp;Lea Nosáľová,&nbsp;Mariana Kolesárová,&nbsp;Zuzana Lorková,&nbsp;Nikola Petrová,&nbsp;Peter Pristaš,&nbsp;Jana Kisková","doi":"10.1007/s10534-023-00555-0","DOIUrl":"10.1007/s10534-023-00555-0","url":null,"abstract":"<div><p>The subsurface mine environments characterized by high levels of toxic metals and low nutrient availability represent an extreme threat to bacterial persistence. In recent study, the genomic analysis of the <i>Acinetobacter johnsonii</i> strain RB2-047 isolated from the Rozália Gold Mine in Slovakia was performed. As expected, the studied isolate showed a high level of heavy metal tolerance (minimum inhibitory concentrations were 500 mg/L for copper and nickel, 1,500 mg/L for lead, and 250 mg/L for zinc). The RB2-047 strain also showed noticeable resistance to several antibiotics (ampicillin, kanamycin, chloramphenicol, tetracycline and ciprofloxacin). The genomic composition analysis demonstrated a low number of antibiotic and metal resistance coding genes, but a high occurrence of efflux transporter genes located on the bacterial chromosome. The experimental inhibition of efflux pumps resulted in decreased tolerance to Zn and Ni (but not to Cu and Pb) and to all antibiotics tested. In addition, the H33342 dye-accumulation assay confirmed the high efflux activity in the RB2-047 isolate. These findings showed the important role of efflux pumps in the adaptation of <i>Acinetobacter johsonii</i> strain RB2-047 to metal polluted mine environment as well as in development of multi-antibiotic resistance.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"371 - 387"},"PeriodicalIF":4.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intestinal microbiota protects against methylmercury-induced neurotoxicity 肠道微生物群可防止甲基汞引起的神经毒性。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-16 DOI: 10.1007/s10534-023-00554-1
Tao Ke, André Rajoo, Alexey A. Tinkov, Anatoly V. Skalny, Yousef Tizabi, Joao B. T. Rocha, Aaron B. Bowman, Michael Aschner

Methylmercury (MeHg) remains a global public health issue because of its frequent presence in human food sources obtained from the water. The excretion of MeHg in humans occurs slowly with a biological half-time of 32–47 days. Short-term MeHg exposure may cause long-lasting neurotoxicity. The excretion through feces is a major route in the demethylation of MeHg. Accumulating evidence suggests that the intestinal microbiota plays an important role in the demethylation of MeHg, thereby protecting the host from neurotoxic effects. Here, we discuss recent developments on the role of intestinal microbiota in MeHg metabolism, based on in vitro cell culture experiments, experimental animal studies and human investigations. Demethylation by intestinal bacteria is the rate-limiting step in MeHg metabolism and elimination. The identity of bacteria strains responsible for this biotransformation is currently unknown; however, the non-homogenous distribution of intestinal microbiota may lead to different demethylation rates in the intestinal tract. The maintenance of intestinal barrier function by intestinal microbiota may afford protection against MeHg-induced neurotoxicity, which warrant future investigations. We also discuss studies investigating the effects of MeHg exposure on the population structural stability of intestinal microbiota in several host species. Although this is an emerging area in metal toxicity, current research suggests that a change in certain phyla in the intestinal microbiota may indicate MeHg overexposure.

甲基汞(MeHg)仍然是一个全球公共卫生问题,因为它经常存在于从水中获取的人类食物来源中。人体内甲汞的排泄缓慢,生物半衰期为32-47天。短期接触甲基汞可能造成长期的神经毒性。粪便排泄是甲基汞去甲基化的主要途径。越来越多的证据表明,肠道微生物群在甲基汞的去甲基化中发挥重要作用,从而保护宿主免受神经毒性作用。本文基于体外细胞培养实验、实验动物研究和人体研究,讨论了肠道微生物群在甲基汞代谢中的作用的最新进展。肠道细菌的去甲基化是甲基汞代谢和消除的限速步骤。负责这种生物转化的细菌菌株的身份目前尚不清楚;然而,肠道微生物群的非均匀分布可能导致肠道中不同的去甲基化速率。肠道微生物群维持肠道屏障功能可能对甲基汞诱导的神经毒性具有保护作用,值得进一步研究。我们还讨论了研究甲基汞暴露对几种宿主肠道微生物群结构稳定性的影响。虽然这是金属毒性的一个新兴领域,但目前的研究表明,肠道微生物群中某些门的变化可能表明甲基汞过度暴露。
{"title":"Intestinal microbiota protects against methylmercury-induced neurotoxicity","authors":"Tao Ke,&nbsp;André Rajoo,&nbsp;Alexey A. Tinkov,&nbsp;Anatoly V. Skalny,&nbsp;Yousef Tizabi,&nbsp;Joao B. T. Rocha,&nbsp;Aaron B. Bowman,&nbsp;Michael Aschner","doi":"10.1007/s10534-023-00554-1","DOIUrl":"10.1007/s10534-023-00554-1","url":null,"abstract":"<div><p>Methylmercury (MeHg) remains a global public health issue because of its frequent presence in human food sources obtained from the water. The excretion of MeHg in humans occurs slowly with a biological half-time of 32–47 days. Short-term MeHg exposure may cause long-lasting neurotoxicity. The excretion through feces is a major route in the demethylation of MeHg. Accumulating evidence suggests that the intestinal microbiota plays an important role in the demethylation of MeHg, thereby protecting the host from neurotoxic effects. Here, we discuss recent developments on the role of intestinal microbiota in MeHg metabolism, based on in vitro cell culture experiments, experimental animal studies and human investigations. Demethylation by intestinal bacteria is the rate-limiting step in MeHg metabolism and elimination. The identity of bacteria strains responsible for this biotransformation is currently unknown; however, the non-homogenous distribution of intestinal microbiota may lead to different demethylation rates in the intestinal tract. The maintenance of intestinal barrier function by intestinal microbiota may afford protection against MeHg-induced neurotoxicity, which warrant future investigations. We also discuss studies investigating the effects of MeHg exposure on the population structural stability of intestinal microbiota in several host species. Although this is an emerging area in metal toxicity, current research suggests that a change in certain phyla in the intestinal microbiota may indicate MeHg overexposure.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 3","pages":"561 - 576"},"PeriodicalIF":4.1,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136395655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel vanadyl complexes synthesis, characterization and interactions with bovine serum albumin–effects on STZ- diabetes rats 新型钒基配合物的合成、表征及其与牛血清白蛋白的相互作用对STZ糖尿病大鼠的影响。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-10 DOI: 10.1007/s10534-023-00552-3
Ayub Shaik, Vani Kondaparthy, Alia Begum, Ameena Husain, Tejasree Chinnagalla

Drug-protein interactions are essential since most administered drugs bind abundantly and reversibly to serum albumin and are delivered mainly as a complex with protein. The nature and strength of drug-protein interactions have a big impact on how a drug works biologically. The binding parameters are useful in studying the pharmacological response of drugs and the designing of dosage forms. Serum albumin is regarded as optimal model for in vitro research on drug-protein interaction since it is the main protein that binds medicines and other physiological components. In this perspective, binary complex have been synthesized and characterized, from vanadium metal and acetylacetone(4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione). Imidazole, 2-Methyl-imidazole, and 2-Ethyl-imidazole auxiliary ligands were employed for the synthesis of ternary complexes. Additionally, UV absorption and fluorescence emission spectroscopy were used to examine the binding interactions between vanadium complexes and Bovine Serum Albumin. The outcomes of the binding studies and spectral approaches were in strong agreement with one another. These complexes upon inoculation into diabetes-induced Wistar rats stabilized their serum glucose levels within 3 days. From various studies, it was discovered that the ordering of glucose-lowering actions of these metal complexes were equivalent. The vanadium ternary metal complex derived from (4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione) and imidazole as ligands is the best among the other metal vanadium complexes.

药物-蛋白质相互作用是至关重要的,因为大多数给药药物与血清白蛋白充分可逆地结合,并且主要以与蛋白质的复合物的形式递送。药物-蛋白质相互作用的性质和强度对药物的生物学作用有很大影响。结合参数可用于研究药物的药理学反应和剂型设计。血清白蛋白是结合药物和其他生理成分的主要蛋白质,因此被认为是体外研究药物与蛋白质相互作用的最佳模型。从这个角度出发,以金属钒和乙酰丙酮(4,4,4-三氟-1-(2-噻吩基)-1,3-丁二酮)为原料,合成并表征了二元配合物。咪唑、2-甲基咪唑和2-乙基咪唑辅助配体用于合成三元配合物。此外,还利用紫外吸收光谱和荧光发射光谱研究了钒配合物与牛血清白蛋白之间的结合相互作用。约束性研究和光谱方法的结果彼此非常一致。这些复合物在接种到糖尿病诱导的Wistar大鼠中后在3天内稳定了它们的血清葡萄糖水平。从各种研究中发现,这些金属配合物的降血糖作用的顺序是相等的。以(4,4,4-三氟-1-(2-噻吩基)-1,3-丁二酮)和咪唑为配体的钒三元金属配合物是其他金属钒配合物中最好的。
{"title":"Novel vanadyl complexes synthesis, characterization and interactions with bovine serum albumin–effects on STZ- diabetes rats","authors":"Ayub Shaik,&nbsp;Vani Kondaparthy,&nbsp;Alia Begum,&nbsp;Ameena Husain,&nbsp;Tejasree Chinnagalla","doi":"10.1007/s10534-023-00552-3","DOIUrl":"10.1007/s10534-023-00552-3","url":null,"abstract":"<div><p>Drug-protein interactions are essential since most administered drugs bind abundantly and reversibly to serum albumin and are delivered mainly as a complex with protein. The nature and strength of drug-protein interactions have a big impact on how a drug works biologically. The binding parameters are useful in studying the pharmacological response of drugs and the designing of dosage forms. Serum albumin is regarded as optimal model for in vitro research on drug-protein interaction since it is the main protein that binds medicines and other physiological components. In this perspective, binary complex have been synthesized and characterized, from vanadium metal and acetylacetone(4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione). Imidazole, 2-Methyl-imidazole, and 2-Ethyl-imidazole auxiliary ligands were employed for the synthesis of ternary complexes. Additionally, UV absorption and fluorescence emission spectroscopy were used to examine the binding interactions between vanadium complexes and Bovine Serum Albumin. The outcomes of the binding studies and spectral approaches were in strong agreement with one another. These complexes upon inoculation into diabetes-induced Wistar rats stabilized their serum glucose levels within 3 days. From various studies, it was discovered that the ordering of glucose-lowering actions of these metal complexes were equivalent. The vanadium ternary metal complex derived from (4,4,4-trifluoro-1-(2-theonyl)-1,3-butanedione) and imidazole as ligands is the best among the other metal vanadium complexes.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"357 - 369"},"PeriodicalIF":4.1,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72012974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the antimalarial and antioxidant efficacy of transition metal(II) chelates of thiosemicarbazone ligands: spectral investigations, molecular docking, DFT, MESP and ADMET 探索氨基硫脲配体的过渡金属(II)螯合物的抗疟和抗氧化功效:光谱研究、分子对接、DFT、MESP和ADMET。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-08 DOI: 10.1007/s10534-023-00546-1
Jai Devi, Binesh Kumar, Amit Dubey, Aisha Tufail, Ankit Boora

Malaria, a relentless and ancient adversary, continues to cast its shadow over vast swathes of the globe, afflicting millions of people and have a heavy toll on human health and well-being. Despite substantial progress in the fight against this parasitic disease in recent decades, malaria still persists as a substantial global health concern, especially in some specific region which have limited resources and vulnerable populations. Thus, to ascertain an combating agent for malaria and its associated dysfunction, 4-(4-ethylphenyl)-3-thiosemicarbazide and benzaldehydes based two new thiosemicarbazone ligands (1–2) and their cobalt(II), nickel(II), copper(II), zinc(II) metal complexes (3–10) were synthesized in the present research work. The synthesized compounds were comprehensive characterized through spectral and physical investigations, demonstrating octahedral stereochemistry of the complexes. Further, the antimalarial and antioxidant potential of the compounds (1–10) were analyzed by micro assay and DPPH assay protocols, respectively, to examine the therapeutic aspect of the compounds. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. The complexes (5), (6), (10) shows significant efficiency for malarial and oxidant dysfunctions whereas Zn(II) complex (6) exhibit highest potency with 1.02 ± 0.07 and 2.28 ± 0.05 µM IC50 value. Furthermore, to support the highest antimalarial potency of the (3–6) complexes and their associated ligand (1), the computational studies like molecular docking, DFT, MESP and ADMET analysis were executed which were supported the biological efficacy of the complex (6) by providing numerous parameters like binding interaction electronegativity, electrophilicity, HOMO value and electron density.

疟疾是一个无情而古老的对手,它继续给全球大片地区蒙上阴影,困扰着数百万人,并对人类健康和福祉造成严重损失。尽管近几十年来在防治这种寄生虫病方面取得了重大进展,但疟疾仍然是一个严重的全球健康问题,特别是在一些资源有限、人口脆弱的特定地区。因此,为了确定疟疾及其相关功能障碍的防治剂,本研究合成了基于4-(4-乙基苯基)-3-氨基硫脲和苯甲醛的两种新的氨基硫脲配体(1-2)及其钴(II)、镍(II),铜(II)和锌(II)金属络合物(3-10)。通过光谱和物理研究对合成的化合物进行了综合表征,证明了配合物的八面体立体化学性质。此外,分别通过微量分析和DPPH分析方案分析化合物(1-10)的抗疟和抗氧化潜力,以检查化合物的治疗方面。进行的生物学评估表明,与配体相比,复合物在控制感染性疾病方面更有效。配合物(5)、(6)、(10)对疟疾和氧化剂功能障碍显示出显著的效率,而Zn(II)配合物(6)显示出最高的效力,为1.02 ± 0.07和2.28 ± 0.05µM IC50值。此外,为了支持(3-6)复合物及其相关配体(1)的最高抗疟效力,进行了分子对接、DFT、MESP和ADMET分析等计算研究,通过提供许多参数,如结合相互作用电负性、亲电性、HOMO值和电子密度,支持了复合物(6)的生物学功效。
{"title":"Exploring the antimalarial and antioxidant efficacy of transition metal(II) chelates of thiosemicarbazone ligands: spectral investigations, molecular docking, DFT, MESP and ADMET","authors":"Jai Devi,&nbsp;Binesh Kumar,&nbsp;Amit Dubey,&nbsp;Aisha Tufail,&nbsp;Ankit Boora","doi":"10.1007/s10534-023-00546-1","DOIUrl":"10.1007/s10534-023-00546-1","url":null,"abstract":"<div><p>Malaria, a relentless and ancient adversary, continues to cast its shadow over vast swathes of the globe, afflicting millions of people and have a heavy toll on human health and well-being. Despite substantial progress in the fight against this parasitic disease in recent decades, malaria still persists as a substantial global health concern, especially in some specific region which have limited resources and vulnerable populations. Thus, to ascertain an combating agent for malaria and its associated dysfunction, 4-(4-ethylphenyl)-3-thiosemicarbazide and benzaldehydes based two new thiosemicarbazone ligands (1–2) and their cobalt(II), nickel(II), copper(II), zinc(II) metal complexes (3–10) were synthesized in the present research work. The synthesized compounds were comprehensive characterized through spectral and physical investigations, demonstrating octahedral stereochemistry of the complexes. Further, the antimalarial and antioxidant potential of the compounds (1–10) were analyzed by micro assay and DPPH assay protocols, respectively, to examine the therapeutic aspect of the compounds. The performed biological evaluations revealed that the complexes are more efficient in controlling infectious ailment in comparison of ligands. The complexes (5), (6), (10) shows significant efficiency for malarial and oxidant dysfunctions whereas Zn(II) complex (6) exhibit highest potency with 1.02 ± 0.07 and 2.28 ± 0.05 µM IC<sub>50</sub> value. Furthermore, to support the highest antimalarial potency of the (3–6) complexes and their associated ligand (1), the computational studies like molecular docking, DFT, MESP and ADMET analysis were executed which were supported the biological efficacy of the complex (6) by providing numerous parameters like binding interaction electronegativity, electrophilicity, HOMO value and electron density.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 1","pages":"247 - 265"},"PeriodicalIF":4.1,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tyrosine kinase inhibitors (TKIs) for ovarian cancer treatment: from organic to inorganic chemotherapeutics towards selectivity—a perspective overview 酪氨酸激酶抑制剂(TKIs)用于卵巢癌症治疗:从有机化学治疗到无机化学治疗的选择性——透视综述。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-06 DOI: 10.1007/s10534-023-00547-0
Emma Baglini, Lorenzo Chiaverini, Iogann Tolbatov, Sabrina Taliani, Federico Da Settimo, Diego La Mendola, Elisabetta Barresi, Tiziano Marzo

Ovarian cancer (OC) is a lethal gynecologic cancer in industrialized countries. Treatments for OC include the surgical removal and chemotherapy. In the last decades, improvements have been made in the surgery technologies, drug combinations and administration protocols, and in diagnosis. However, mortality from OC is still high owing to recurrences and insurgence of drug resistance. Accordingly, it is urgent the development of novel agents capable to effectively target OC. In this respect, tyrosine kinase inhibitors (TKIs) may play an important role. Most of TKIs developed and tested so far are organic. However, owing to their chemical versatility, also metals can be exploited to design selective and potent TKIs. We provide a short and easy-to-read overview on the main organic TKIs with a summary of those that entered clinical trials. Additionally, we describe the potential of metal-based TKIs, focusing on this overlooked family of compounds that may significantly contribute towards the concept of precision-medicine.

癌症(OC)是工业化国家一种致死性的癌症。OC的治疗包括手术切除和化疗。在过去的几十年里,手术技术、药物组合和给药方案以及诊断都有所改进。然而,由于复发和耐药性的增加,OC的死亡率仍然很高。因此,迫切需要开发能够有效靶向OC的新型制剂。在这方面,酪氨酸激酶抑制剂(TKIs)可能发挥重要作用。迄今为止开发和测试的大多数TKI都是有机的。然而,由于其化学通用性,金属也可用于设计选择性和强效TKI。我们提供了一个简短易读的主要有机TKI概述,并对进入临床试验的TKI进行了总结。此外,我们描述了基于金属的TKI的潜力,重点关注这一被忽视的化合物家族,这些化合物可能对精准医学的概念有重大贡献。
{"title":"Tyrosine kinase inhibitors (TKIs) for ovarian cancer treatment: from organic to inorganic chemotherapeutics towards selectivity—a perspective overview","authors":"Emma Baglini,&nbsp;Lorenzo Chiaverini,&nbsp;Iogann Tolbatov,&nbsp;Sabrina Taliani,&nbsp;Federico Da Settimo,&nbsp;Diego La Mendola,&nbsp;Elisabetta Barresi,&nbsp;Tiziano Marzo","doi":"10.1007/s10534-023-00547-0","DOIUrl":"10.1007/s10534-023-00547-0","url":null,"abstract":"<div><p>Ovarian cancer (OC) is a lethal gynecologic cancer in industrialized countries. Treatments for OC include the surgical removal and chemotherapy. In the last decades, improvements have been made in the surgery technologies, drug combinations and administration protocols, and in diagnosis. However, mortality from OC is still high owing to recurrences and insurgence of drug resistance. Accordingly, it is urgent the development of novel agents capable to effectively target OC. In this respect, tyrosine kinase inhibitors (TKIs) may play an important role. Most of TKIs developed and tested so far are organic. However, owing to their chemical versatility, also metals can be exploited to design selective and potent TKIs. We provide a short and easy-to-read overview on the main organic TKIs with a summary of those that entered clinical trials. Additionally, we describe the potential of metal-based TKIs, focusing on this overlooked family of compounds that may significantly contribute towards the concept of precision-medicine.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"275 - 288"},"PeriodicalIF":4.1,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species 新型铜(II)-茶碱/1,10-菲咯啉复合物对耐药念珠菌的抗真菌潜力。
IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-11-02 DOI: 10.1007/s10534-023-00549-y
Heloisa F. Frota, Carolline M. A. Lorentino, Pedro F. Barbosa, Lívia S. Ramos, Iuri C. Barcellos, Lucas Giovanini, Lucieri O. P. Souza, Simone S. C. Oliveira, Olufunso O. Abosede, Adeniyi S. Ogunlaja, Matheus M. Pereira, Marta H. Branquinha, André L. S. Santos

Candida spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-Candida drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of Candida albicans and Candida tropicalis. Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 μg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 μg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)2phen(H2O).5H2O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant Candida species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 μg/mL and MFCs from 15.62 to 62.5 μg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using Galleria mellonella and Tenebrio molitor. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 μg/mL for 5 days. After 24 h of treatment, G. mellonella larvae exhibited high survival rates even when exposed to high doses of CTP (600 μg/mL), with the 50% cytotoxic concentration calculated as 776.2 μg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each Candida species. These findings suggest that CTP could serve as a potential drug to treat infections caused by Candida species resistant to clinically available antifungals.

念珠菌是世界上最常见的真菌病原体。抗真菌耐药性是一个促使发现新型抗念珠菌药物的问题。本文初步评估了25种化合物,其中一些化合物含有铜(II)、钴(II)和锰(II)离子,可抑制白色念珠菌和热带念珠菌参考菌株的生长。八种(32%)化合物抑制了这些酵母的增殖,显示出31.25至250μg/mL的最小抑制浓度(MIC)和62.5至250μg/mL的最小杀真菌浓度(MFCs)。通过SwissADME计算的药物相似性/药代动力学表明,所选的8种化合物适合用作局部药物。配合物CTP,Cu(theo)2phen(H2O).5H2O(theo = 茶碱phen = 选择1,10-菲罗啉)对10种对氟康唑/两性霉素B具有耐药性的医学相关念珠菌进行进一步测试。CTP表现出广谱作用,抑制所有20种临床真菌分离株的生长,MIC为7.81至62.5μg/mL,MFCs为15.62至62.5µg/mL。相反,CTP不会导致红细胞裂解。用香甲藻和黄粉虫对CTP的体内毒性进行了评价。CTP在31.25至250μg/mL的剂量范围内连续5天无毒性或毒性水平低。处理24小时后,即使暴露于高剂量的CTP(600μG/mL),也能显示出较高的存活率,50%的细胞毒性浓度计算为776.2μG/mL,根据每种念珠菌产生的选择性指数在12.4至99.4之间。这些发现表明,CTP可以作为一种潜在的药物来治疗对临床可用抗真菌药物具有耐药性的念珠菌引起的感染。
{"title":"Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species","authors":"Heloisa F. Frota,&nbsp;Carolline M. A. Lorentino,&nbsp;Pedro F. Barbosa,&nbsp;Lívia S. Ramos,&nbsp;Iuri C. Barcellos,&nbsp;Lucas Giovanini,&nbsp;Lucieri O. P. Souza,&nbsp;Simone S. C. Oliveira,&nbsp;Olufunso O. Abosede,&nbsp;Adeniyi S. Ogunlaja,&nbsp;Matheus M. Pereira,&nbsp;Marta H. Branquinha,&nbsp;André L. S. Santos","doi":"10.1007/s10534-023-00549-y","DOIUrl":"10.1007/s10534-023-00549-y","url":null,"abstract":"<div><p><i>Candida</i> spp. are the commonest fungal pathogens worldwide. Antifungal resistance is a problem that has prompted the discovery of novel anti-<i>Candida</i> drugs. Herein, 25 compounds, some of them containing copper(II), cobalt(II) and manganese(II) ions, were initially evaluated for inhibiting the growth of reference strains of <i>Candida albicans</i> and <i>Candida tropicalis.</i> Eight (32%) of the compounds inhibited the proliferation of these yeasts, displaying minimum inhibitory concentrations (MICs) ranging from 31.25 to 250 μg/mL and minimum fungicidal concentration (MFCs) from 62.5 to 250 μg/mL. Drug-likeness/pharmacokinetic calculated by SwissADME indicated that the 8 selected compounds were suitable for use as topical drugs. The complex CTP, Cu(theo)<sub>2</sub>phen(H<sub>2</sub>O).5H<sub>2</sub>O (theo = theophylline; phen = 1,10-phenanthroline), was chosen for further testing against 10 medically relevant <i>Candida</i> species that were resistant to fluconazole/amphotericin B. CTP demonstrated a broad spectrum of action, inhibiting the growth of all 20 clinical fungal isolates, with MICs from 7.81 to 62.5 μg/mL and MFCs from 15.62 to 62.5 μg/mL. Conversely, CTP did not cause lysis in erythrocytes. The toxicity of CTP was evaluated in vivo using <i>Galleria mellonella</i> and <i>Tenebrio molitor</i>. CTP had no or low levels of toxicity at doses ranging from 31.25 to 250 μg/mL for 5 days. After 24 h of treatment, <i>G. mellonella</i> larvae exhibited high survival rates even when exposed to high doses of CTP (600 μg/mL), with the 50% cytotoxic concentration calculated as 776.2 μg/mL, generating selectivity indexes varying from 12.4 to 99.4 depending on each <i>Candida</i> species. These findings suggest that CTP could serve as a potential drug to treat infections caused by <i>Candida</i> species resistant to clinically available antifungals.</p></div>","PeriodicalId":491,"journal":{"name":"Biometals","volume":"37 2","pages":"321 - 336"},"PeriodicalIF":4.1,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Biometals
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1