Mohammed Al-Zharani, Abdullah A. Alkahtane, Norah S. AL-Johani, Bader Almutairi, Nora Alkeraishan, Saud Alarifi, Sahirah M. Alrajeh, Khadijah N. Yaseen, Nada H. Aljarba, Fahd A. Nasr, Saad Alkahtani
Colorectal cancer is known for its substantial impact on global morbidity and mortality, with higher prevalence in developed regions. This study delves into the potential treatment advantages of resveratrol (RSV) in addressing colorectal cancer. Apoptosis and gene expression associated with apoptotic factors were explored using Caco-2 cells, a pertinent model for colorectal adenocarcinoma. The effect of RSV on Caco-2 cell viability was investigated using MTT assay and neutral red uptake assay. The level of generated ROS was high in cells exposed to RSV. Likewise, the enzyme superoxide dismutase, responsible for converting ROS into hydrogen peroxide, was concurrently elevated. The effect of RSV on DNA damage was examined through the TUNEL assay. The gene expression analyses for pro-apoptotic elements were studied using qRT-PCR. Furthermore, the impact of RSV on the migration of Caco-2 cells was conducted through a wound-healing assay. Our results reveal RSV’s cytotoxicity on Caco-2 cells, showing dose-dependent inhibition of viability, indicating its promise as a treatment agent. The induction of cell death by apoptosis is substantiated by DNA damage. Notably, the upregulated expression of caspase-3, Bax, and p53 genes suggests RSV’s potential to modulate key apoptosis-related elements. In addition, RSV displayed an inhibitory effect on cellular migration, a significant (p < 0.05 and p < 0.01) in cancer metastasis. These findings underscore RSV’s potential to be a multifaceted therapeutic agent targeting apoptosis and metastatic processes in colorectal cancer.
{"title":"Investigating the effect of resveratrol on apoptosis and regulation of gene expression of Caco-2 cells: Unravelling potential implications for colorectal cancer treatment","authors":"Mohammed Al-Zharani, Abdullah A. Alkahtane, Norah S. AL-Johani, Bader Almutairi, Nora Alkeraishan, Saud Alarifi, Sahirah M. Alrajeh, Khadijah N. Yaseen, Nada H. Aljarba, Fahd A. Nasr, Saad Alkahtani","doi":"10.1515/chem-2024-0012","DOIUrl":"https://doi.org/10.1515/chem-2024-0012","url":null,"abstract":"Colorectal cancer is known for its substantial impact on global morbidity and mortality, with higher prevalence in developed regions. This study delves into the potential treatment advantages of resveratrol (RSV) in addressing colorectal cancer. Apoptosis and gene expression associated with apoptotic factors were explored using Caco-2 cells, a pertinent model for colorectal adenocarcinoma. The effect of RSV on Caco-2 cell viability was investigated using MTT assay and neutral red uptake assay. The level of generated ROS was high in cells exposed to RSV. Likewise, the enzyme superoxide dismutase, responsible for converting ROS into hydrogen peroxide, was concurrently elevated. The effect of RSV on DNA damage was examined through the TUNEL assay. The gene expression analyses for pro-apoptotic elements were studied using qRT-PCR. Furthermore, the impact of RSV on the migration of Caco-2 cells was conducted through a wound-healing assay. Our results reveal RSV’s cytotoxicity on Caco-2 cells, showing dose-dependent inhibition of viability, indicating its promise as a treatment agent. The induction of cell death by apoptosis is substantiated by DNA damage. Notably, the upregulated expression of caspase-3, Bax, and p53 genes suggests RSV’s potential to modulate key apoptosis-related elements. In addition, RSV displayed an inhibitory effect on cellular migration, a significant (<jats:italic>p</jats:italic> < 0.05 and <jats:italic>p</jats:italic> < 0.01) in cancer metastasis. These findings underscore RSV’s potential to be a multifaceted therapeutic agent targeting apoptosis and metastatic processes in colorectal cancer.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"50 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Naveed, Noor ul Ain, Tariq Aziz, Ayesha Saleem, Muhammad Aqib Shabbir, Ayaz Ali Khan, Thamer H. Albekairi
Naegleria fowleri is a free-living amoeba that causes primary amoebic meningoencephalitis. Despite combination drug therapies, N. fowleri is not sensitive to current drug therapies, contributing to the pathogen’s mortality rate of 98%. To enable rational drug designing, this study has proposed an integrated track of nanotechnology coupling with the enrichment concept. In the current study, zinc oxide nanoparticles (ZNP) were screened against ERK protein, which is responsible for the production of pro-inflammatory cytokines that cause brain disturbance in N. fowleri infection. Furthermore, an enrichment analysis has been executed to increase the efficiency of the ZNP through the addition of two amines and one chlorine group. The computational prediction of zeta potential, cytotoxicity, organ toxicity, calculations of binding free energy, and ADMET analysis shows that it is stable and possesses no toxic effect. Amine + chlorine enriched ZNP resulted in a binding energy of −7.8 kcal/mol, a zeta potential reliability of −40 mV, a cytotoxicity of −0.0002, inactive against all the targeted organ models, ADMET profiling shows a molecular weight of 320.54 g/mol, a lipophilicity of −0.99, high water solubility, and good gastrointestinal tract absorption. This proposed invention represents the future work for in vitro in combating this devastating disease toward a reliable therapeutic target with drugs that specifically aimed to inhibit the infection.
{"title":"Integrated track of nano-informatics coupling with the enrichment concept in developing a novel nanoparticle targeting ERK protein in Naegleria fowleri","authors":"Muhammad Naveed, Noor ul Ain, Tariq Aziz, Ayesha Saleem, Muhammad Aqib Shabbir, Ayaz Ali Khan, Thamer H. Albekairi","doi":"10.1515/chem-2023-0198","DOIUrl":"https://doi.org/10.1515/chem-2023-0198","url":null,"abstract":"<jats:italic>Naegleria fowleri</jats:italic> is a free-living amoeba that causes primary amoebic meningoencephalitis. Despite combination drug therapies, <jats:italic>N. fowleri</jats:italic> is not sensitive to current drug therapies, contributing to the pathogen’s mortality rate of 98%. To enable rational drug designing, this study has proposed an integrated track of nanotechnology coupling with the enrichment concept. In the current study, zinc oxide nanoparticles (ZNP) were screened against ERK protein, which is responsible for the production of pro-inflammatory cytokines that cause brain disturbance in <jats:italic>N. fowleri infection.</jats:italic> Furthermore, an enrichment analysis has been executed to increase the efficiency of the ZNP through the addition of two amines and one chlorine group. The computational prediction of zeta potential, cytotoxicity, organ toxicity, calculations of binding free energy, and ADMET analysis shows that it is stable and possesses no toxic effect. Amine + chlorine enriched ZNP resulted in a binding energy of −7.8 kcal/mol, a zeta potential reliability of −40 mV, a cytotoxicity of −0.0002, inactive against all the targeted organ models, ADMET profiling shows a molecular weight of 320.54 g/mol, a lipophilicity of −0.99, high water solubility, and good gastrointestinal tract absorption. This proposed invention represents the future work for in vitro in combating this devastating disease toward a reliable therapeutic target with drugs that specifically aimed to inhibit the infection.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"49 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The recent research was done to assess the hematological and biochemical disorders in nephrotoxicity induced by gentamicin (100 mg/kg) in Wistar rats. The green-formulated silver nanoparticles (AgNPs) by Tribulus terrestris leaf were analyzed by XRD, energy-dispersive X-ray spectrometer, and field emission scanning electron microscopy. The shape of the recent nanoparticles was spherical in size of 48 nm. In the in vivo, the classical and novel kidney injury parameters were used to assess the nephroprotective properties of AgNPs in animal model. Gentamicin decreased significantly (P ≤ 0.01) the value of PCV, concentration of HB, and count of RBC. The value of serum iron, erythropoietin, Cr, and urea raised in the gentamicin group. Leucogram revealed thrombocytopenia, granulocytosis, and leukocytosis. AgNPs improved the iron, erythropoietin, thrombocytes, leukogram, and erythrogram. The levels of creatinine, urea, GGT, ALT, AST, and ALP significantly reduced and albumin and total protein increased in group treated with AgNPs. Also, AgNPs significantly raised the anti-inflammatory cytokines, i.e., IL3, TGFβ, IL10, IL5, and IL4, and decreased the pro-inflammatory cytokines, i.e., TNFα, IL18, IL12, IL6, and IL1. These findings may offer AgNPs as a nephroprotective agent that could be a suitable therapeutic supplement in blood disorders conditions.
{"title":"Iron indices and hemogram in renal anemia and the improvement with Tribulus terrestris green-formulated silver nanoparticles applied on rat model","authors":"Xiujuan Wu, Jingyan Shi, Yangping Dai, Weiqi Tang, Huijun Cao, Jieyu Chen","doi":"10.1515/chem-2023-0212","DOIUrl":"https://doi.org/10.1515/chem-2023-0212","url":null,"abstract":"The recent research was done to assess the hematological and biochemical disorders in nephrotoxicity induced by gentamicin (100 mg/kg) in Wistar rats. The green-formulated silver nanoparticles (AgNPs) by <jats:italic>Tribulus terrestris</jats:italic> leaf were analyzed by XRD, energy-dispersive X-ray spectrometer, and field emission scanning electron microscopy. The shape of the recent nanoparticles was spherical in size of 48 nm. In the <jats:italic>in vivo</jats:italic>, the classical and novel kidney injury parameters were used to assess the nephroprotective properties of AgNPs in animal model. Gentamicin decreased significantly (<jats:italic>P</jats:italic> ≤ 0.01) the value of PCV, concentration of HB, and count of RBC. The value of serum iron, erythropoietin, Cr, and urea raised in the gentamicin group. Leucogram revealed thrombocytopenia, granulocytosis, and leukocytosis. AgNPs improved the iron, erythropoietin, thrombocytes, leukogram, and erythrogram. The levels of creatinine, urea, GGT, ALT, AST, and ALP significantly reduced and albumin and total protein increased in group treated with AgNPs. Also, AgNPs significantly raised the anti-inflammatory cytokines, i.e., IL3, TGFβ, IL10, IL5, and IL4, and decreased the pro-inflammatory cytokines, i.e., TNFα, IL18, IL12, IL6, and IL1. These findings may offer AgNPs as a nephroprotective agent that could be a suitable therapeutic supplement in blood disorders conditions.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"49 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is known that one of the greatest problems of developed countries in the twenty-first century is traffic. For this reason, engineers have searched for alternative solutions to the problem of traffic. One such solution is the construction and utilization of rail systems instead of main roads. From an engineering perspective, rail systems can be divided into three groups: metro, light metro, and tram systems. Light metro systems, which are a form of public transportation, are not directly inside the traffic. Their most important advantages include the fact that they do not release combustion products such as CO, and metro and light metro systems may be considered environmentally friendly based solely on their electricity consumption. In this study, measurements of parameters affecting indoor air quality were made inside light metro cars and in and around light metro stations belonging to the light metro system of the Metropolitan Municipality of Antalya, known as the tourism capital of Turkey. In February and March 2021, when the COVID-19 pandemic was first registered in Turkey, particulate matter (PM), temperature, and relative humidity measurements were made for testing indoor and outside air quality. Moreover, as outside air parameters, outside temperature, outside relative humidity, CO, normalized difference vegetation index, and ultraviolet aerosol index data were obtained from the General Directorate of Meteorology of Turkey. The measurement results were analyzed using the inverse distance weighting method in the geographic information system. Based on the results of the analyses, spatial maps were created for indoor and outside air quality parameters in the light metro system. Using these maps, the effects of passenger density and environmental factors both inside the metro cars and at the metro stations on indoor air quality were identified. In addition, the spread of the SARS-CoV-2 virus in the COVID-19 period was analyzed using spatial maps of the PM0.3 and PM0.5 parameters. It is believed that the results of this study will set an example for further indoor air quality studies worldwide, and this study is unique in that it employed a method that is used particularly in survey and geomatics engineering for analyzing indoor air quality in light metro systems.
{"title":"Spatial mapping of indoor air quality in a light metro system using the geographic information system method","authors":"Ahmet Çoşgun","doi":"10.1515/chem-2023-0208","DOIUrl":"https://doi.org/10.1515/chem-2023-0208","url":null,"abstract":"It is known that one of the greatest problems of developed countries in the twenty-first century is traffic. For this reason, engineers have searched for alternative solutions to the problem of traffic. One such solution is the construction and utilization of rail systems instead of main roads. From an engineering perspective, rail systems can be divided into three groups: metro, light metro, and tram systems. Light metro systems, which are a form of public transportation, are not directly inside the traffic. Their most important advantages include the fact that they do not release combustion products such as CO, and metro and light metro systems may be considered environmentally friendly based solely on their electricity consumption. In this study, measurements of parameters affecting indoor air quality were made inside light metro cars and in and around light metro stations belonging to the light metro system of the Metropolitan Municipality of Antalya, known as the tourism capital of Turkey. In February and March 2021, when the COVID-19 pandemic was first registered in Turkey, particulate matter (PM), temperature, and relative humidity measurements were made for testing indoor and outside air quality. Moreover, as outside air parameters, outside temperature, outside relative humidity, CO, normalized difference vegetation index, and ultraviolet aerosol index data were obtained from the General Directorate of Meteorology of Turkey. The measurement results were analyzed using the inverse distance weighting method in the geographic information system. Based on the results of the analyses, spatial maps were created for indoor and outside air quality parameters in the light metro system. Using these maps, the effects of passenger density and environmental factors both inside the metro cars and at the metro stations on indoor air quality were identified. In addition, the spread of the SARS-CoV-2 virus in the COVID-19 period was analyzed using spatial maps of the PM<jats:sub>0.3</jats:sub> and PM<jats:sub>0.5</jats:sub> parameters. It is believed that the results of this study will set an example for further indoor air quality studies worldwide, and this study is unique in that it employed a method that is used particularly in survey and geomatics engineering for analyzing indoor air quality in light metro systems.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"49 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shoaib Khan, Rafaqat Hussain, Yousaf Khan, Tayyiaba Iqbal, Tariq Aziz, Metab Alharbi
In the current era, a potent drug is still needed on the market for the treatment of various diseases worldwide. Researchers mainly focus on those enzymes that cause these diseases. One of the major diseases is caused by an enzyme called urease, which increases the concentration of ammonia in the body upon hydrolysis. Researchers across the globe have keen interest to synthesize the potent inhibitor for this conversion. From this perspective, hybrid analogs of imidazopyridine and oxadiazole (1–20) were designed and efficiently synthesized followed by characterizing them through varied spectroscopic methods (1HNMR, 13CNMR, and HREI-MS). In addition, in vitro analyses of the synthesized compounds were conducted to evaluate their anti-urease potency. There was significant potential in most compounds analyzed, but analogs 15, 16, and 17 (IC50 = 2.20 ± 0.10 μM, IC50 = 2.50 ± 0.10 μM, and IC50 = 2.30 ± 2.10 μM, respectively) performed exceptionally well in comparison with thiourea (IC50 = 22.30 ± 0.44 μM). The selected candidates were further investigated under a molecular docking study to confirm protein ligand interactions. In addition, energy gap (Egap) of the HOMO–LUMO was explored via density functional theory studies.
{"title":"Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives","authors":"Shoaib Khan, Rafaqat Hussain, Yousaf Khan, Tayyiaba Iqbal, Tariq Aziz, Metab Alharbi","doi":"10.1515/chem-2023-0210","DOIUrl":"https://doi.org/10.1515/chem-2023-0210","url":null,"abstract":"In the current era, a potent drug is still needed on the market for the treatment of various diseases worldwide. Researchers mainly focus on those enzymes that cause these diseases. One of the major diseases is caused by an enzyme called urease, which increases the concentration of ammonia in the body upon hydrolysis. Researchers across the globe have keen interest to synthesize the potent inhibitor for this conversion. From this perspective, hybrid analogs of imidazopyridine and oxadiazole (1–20) were designed and efficiently synthesized followed by characterizing them through varied spectroscopic methods (<jats:sup>1</jats:sup>HNMR, <jats:sup>13</jats:sup>CNMR, and HREI-MS). In addition, <jats:italic>in vitro</jats:italic> analyses of the synthesized compounds were conducted to evaluate their anti-urease potency. There was significant potential in most compounds analyzed, but analogs 15, 16, and 17 (IC<jats:sub>50</jats:sub> = 2.20 ± 0.10 μM, IC<jats:sub>50</jats:sub> = 2.50 ± 0.10 μM, and IC<jats:sub>50</jats:sub> = 2.30 ± 2.10 μM, respectively) performed exceptionally well in comparison with thiourea (IC<jats:sub>50</jats:sub> = 22.30 ± 0.44 μM). The selected candidates were further investigated under a molecular docking study to confirm protein ligand interactions. In addition, energy gap (<jats:italic>E</jats:italic> <jats:sub>gap</jats:sub>) of the HOMO–LUMO was explored via density functional theory studies.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"33 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kamal Hassan Suliman, Abdel-Rhman Z. Gaafar, Abdelmalik M. Abdelmalik, Bandar M. AlMunqedhi, Abdalla Elzein, Mohamed S. Hodhod
The dehydrogenase activity (DHA) in the rhizospheres of tomatoes grown in different soil types – Khor Abu-Habil (KA), Bara (B), and Greenhouse (Gr) – in North Kordofan, Sudan, was determined. In addition, the abundance of soil microbes in the tomato rhizospheres during the two growth stages, after 45 and 90 days (short and long term), was analyzed. The KA site (clay soil) showed the highest DHA (81.79 CFUs/g) followed by the B site (63.76 CFUs/g) (sandy loam) after 90 days of sowing, and the Gr site showed the lowest DHA (44.50 CFUs/g) (loamy sand soil) after 45 days. Moreover, the presence of high microbial activity (total density counts, total fungi, phosphate-solubilizing bacteria, Streptomycetes sp., Azotobacter sp., Azospirillum sp., and Pseudomonas sp. density counts) after 90 days and minimum microbial abundance after 45 days were identified at all sites. The measured growth parameters of fresh and dry weight, in addition to the root-to-shoot ratio, increased significantly at the same KA site dominated by a higher microbial density after 90 days. During the long term, the growth stage was positively affected by the abundance of adapted microbials that improve and enhance plant growth.
本研究测定了在苏丹北科尔多凡州不同土壤类型--Khor Abu-Habil（KA）、Bara（B）和Greenhouse（Gr）--种植的番茄根瘤中的脱氢酶活性（DHA）。此外，还分析了在 45 天和 90 天（短期和长期）两个生长阶段番茄根瘤中土壤微生物的丰度。播种 90 天后，KA 地块（粘土）的 DHA 最高（81.79 CFUs/g），其次是 B 地块（沙壤土）（63.76 CFUs/g），而 Gr 地块（壤土）45 天后的 DHA 最低（44.50 CFUs/g）。此外，所有地点在 90 天后都出现了较高的微生物活性（总密度计数、真菌总数、磷酸盐溶解菌、链霉菌属 sp.、氮杂菌属 sp.、氮基螺旋菌属 sp.和假单胞菌属 sp.密度计数），45 天后微生物丰度最低。90 天后，在同一个 KA 地点，由于微生物密度较高，鲜重和干重以及根芽比等测量生长参数显著增加。从长期来看，生长阶段受到适应性微生物丰度的积极影响，这些微生物可改善和促进植物生长。
{"title":"Microbial dynamics and dehydrogenase activity in tomato (Lycopersicon esculentum Mill.) rhizospheres: Impacts on growth and soil health across different soil types","authors":"Kamal Hassan Suliman, Abdel-Rhman Z. Gaafar, Abdelmalik M. Abdelmalik, Bandar M. AlMunqedhi, Abdalla Elzein, Mohamed S. Hodhod","doi":"10.1515/chem-2023-0209","DOIUrl":"https://doi.org/10.1515/chem-2023-0209","url":null,"abstract":"The dehydrogenase activity (DHA) in the rhizospheres of tomatoes grown in different soil types – Khor Abu-Habil (KA), Bara (B), and Greenhouse (Gr) – in North Kordofan, Sudan, was determined. In addition, the abundance of soil microbes in the tomato rhizospheres during the two growth stages, after 45 and 90 days (short and long term), was analyzed. The KA site (clay soil) showed the highest DHA (81.79 CFUs/g) followed by the B site (63.76 CFUs/g) (sandy loam) after 90 days of sowing, and the Gr site showed the lowest DHA (44.50 CFUs/g) (loamy sand soil) after 45 days. Moreover, the presence of high microbial activity (total density counts, total fungi, phosphate-solubilizing bacteria, <jats:italic>Streptomycetes</jats:italic> sp., <jats:italic>Azotobacter</jats:italic> sp., <jats:italic>Azospirillum</jats:italic> sp., and <jats:italic>Pseudomonas</jats:italic> sp. density counts) after 90 days and minimum microbial abundance after 45 days were identified at all sites. The measured growth parameters of fresh and dry weight, in addition to the root-to-shoot ratio, increased significantly at the same KA site dominated by a higher microbial density after 90 days. During the long term, the growth stage was positively affected by the abundance of adapted microbials that improve and enhance plant growth.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"26 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140311686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Somdutt Mujwar, Jyoti Pal, Manu Sharma, Abhishek Tiwari, Varsha Tiwari, Manish Kumar, Shivani Verma, Ashraf Ahmed Qurtam, Fahd A. Nasr, Mohammed Al-Zharani, Abdulsalam Alhalmi
Dengue virus (DENV) infection is one of the diseases for which no drug is available for the treatment. The DENV NS2B-NS3 protease is considered to be the prime target for anti-dengue drug development because of its importance in the development of new virus subunits via DENV poly-protein breakdown. Pentacyclic triterpenoids (Lantadenes) from the weed Lantana camara L. and its semi-synthetic congeners have shown a wide array of biological activities in the last two decades. The virtual screening strategy was used on the library of 78 natural and semi-synthetic lantadenes to predict the potent antagonists for the NS2B-NS3 protease enzyme of DENV and their experimental validation by in vitro assay of lead molecules. In the in silico analysis of 78 triterpenoids, two lead molecules (−10.60 and −9.93 kcal/mol) were predicted to be inhibitors of protease (viral) when compared to its reference ligand 1,8-dihydroxy-4,5-dinitroanthraquinone (−5.377 kcal/mol). At the same time, binding affinity, pharmacokinetic, and toxicity profiling, along with molecular dynamics simulations, were studied. The in vitro viral infection inhibition assay inferred that lead molecule 62 exhibited a 60% and 45% reduction in DENV titers at 10 and 5 µM concentrations, respectively. The lead molecule 62 can further be optimized for its pharmacophore and has the potential to be developed as a drug-like molecule.
{"title":"Computational design and in vitro assay of lantadene-based novel inhibitors of NS3 protease of dengue virus","authors":"Somdutt Mujwar, Jyoti Pal, Manu Sharma, Abhishek Tiwari, Varsha Tiwari, Manish Kumar, Shivani Verma, Ashraf Ahmed Qurtam, Fahd A. Nasr, Mohammed Al-Zharani, Abdulsalam Alhalmi","doi":"10.1515/chem-2024-0004","DOIUrl":"https://doi.org/10.1515/chem-2024-0004","url":null,"abstract":"Dengue virus (DENV) infection is one of the diseases for which no drug is available for the treatment. The DENV NS2B-NS3 protease is considered to be the prime target for anti-dengue drug development because of its importance in the development of new virus subunits via DENV poly-protein breakdown. Pentacyclic triterpenoids (Lantadenes) from the weed <jats:italic>Lantana camara</jats:italic> L. and its semi-synthetic congeners have shown a wide array of biological activities in the last two decades. The virtual screening strategy was used on the library of 78 natural and semi-synthetic lantadenes to predict the potent antagonists for the NS2B-NS3 protease enzyme of DENV and their experimental validation by <jats:italic>in vitro</jats:italic> assay of lead molecules. In the <jats:italic>in silico</jats:italic> analysis of 78 triterpenoids, two lead molecules (−10.60 and −9.93 kcal/mol) were predicted to be inhibitors of protease (viral) when compared to its reference ligand 1,8-dihydroxy-4,5-dinitroanthraquinone (−5.377 kcal/mol). At the same time, binding affinity, pharmacokinetic, and toxicity profiling, along with molecular dynamics simulations, were studied. The <jats:italic>in vitro</jats:italic> viral infection inhibition assay inferred that lead molecule 62 exhibited a 60% and 45% reduction in DENV titers at 10 and 5 µM concentrations, respectively. The lead molecule 62 can further be optimized for its pharmacophore and has the potential to be developed as a drug-like molecule.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"365 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140203712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naser F. Al-Tannak, John V. Anyam, Eman Y. Santali, Alexander I. Gray, Collins U. Ibeji, John O. Igoli
A new labdane diterpene characterized as 18α-O-trans-p-feruloyl-15-methyl-8(17)-labdanoate has been isolated from the roots of Vachellia nilotica. Also isolated were p-coumaric acid, ferulic acid, stearic acid, lupeol, and a mixture of β-sitosterol and stigmasterol. The compounds were obtained after a series of column chromatography on silica gel, and their structures were elucidated using NMR and LC-MS analyses. The new diterpene showed good anti-parasitic activity with an IC50 of 0.0177 µM against Trypanosoma brucei and 0.0154 µM against Leishmania major using an Alamar Blue assay. The compound also displayed very good inhibitory activity against Leishmania major compared to Trypanosoma brucei rhodesiense with a binding energy of −10.5 and −7.8 kcal/mol, respectively. Density functional theory analysis showed that the studied compound has low LUMO–HOMO energy, signifying a high chemical reactivity with the ability to donate electrons to electron-accepting species.
{"title":"Anti-parasitic activity and computational studies on a novel labdane diterpene from the roots of Vachellia nilotica","authors":"Naser F. Al-Tannak, John V. Anyam, Eman Y. Santali, Alexander I. Gray, Collins U. Ibeji, John O. Igoli","doi":"10.1515/chem-2024-0005","DOIUrl":"https://doi.org/10.1515/chem-2024-0005","url":null,"abstract":"A new labdane diterpene characterized as 18α-<jats:italic>O</jats:italic>-<jats:italic>trans</jats:italic>-<jats:italic>p</jats:italic>-feruloyl-15-methyl-8(17)-labdanoate has been isolated from the roots of <jats:italic>Vachellia nilotica</jats:italic>. Also isolated were <jats:italic>p</jats:italic>-coumaric acid, ferulic acid, stearic acid, lupeol, and a mixture of β-sitosterol and stigmasterol. The compounds were obtained after a series of column chromatography on silica gel, and their structures were elucidated using NMR and LC-MS analyses. The new diterpene showed good anti-parasitic activity with an IC<jats:sub>50</jats:sub> of 0.0177 µM against <jats:italic>Trypanosoma brucei</jats:italic> and 0.0154 µM against <jats:italic>Leishmania major</jats:italic> using an Alamar Blue assay. The compound also displayed very good inhibitory activity against <jats:italic>Leishmania major</jats:italic> compared to <jats:italic>Trypanosoma brucei rhodesiense</jats:italic> with a binding energy of −10.5 and −7.8 kcal/mol, respectively. Density functional theory analysis showed that the studied compound has low LUMO–HOMO energy, signifying a high chemical reactivity with the ability to donate electrons to electron-accepting species.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"31 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140203708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This article covers 26 Pt(<jats:sc>ii</jats:sc>) complexes of compositions Pt(η<jats:sup>3</jats:sup>-X<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>X<jats:sup>2</jats:sup>)(PL) (X<jats:sup>1,2</jats:sup> = O, C, or Se) and Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>X<jats:sup>1</jats:sup>)(PL) (X<jats:sup>1</jats:sup> = C, S, or Se). These complexes crystallized in two crystal classes: monoclinic (14 examples) and triclinic (12 examples). The heterotridentate ligand with monodentate PL builds up a distorted square-planar geometry around each Pt(<jats:sc>ii</jats:sc>) atom. Each heterotridentate ligand Pt(η<jats:sup>3</jats:sup>-X<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>X<jats:sup>2</jats:sup>)(PL) creates two metallocyclic rings with a common N<jats:sup>1</jats:sup> atom of the O<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>O<jats:sup>2</jats:sup>, O<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>N<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>O<jats:sup>2</jats:sup>, O<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>NN<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>O<jats:sup>2</jats:sup>, C<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>C<jats:sup>2</jats:sup>, and Se<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>1</jats:sup>NC<jats:sub>2</jats:sub>Se<jats:sup>2</jats:sup> types. In Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>X<jats:sup>1</jats:sup>)(PL) complexes, the tridentate ligand with a common N<jats:sup>2</jats:sup> atom forms the following types of metallocyclic rings: N<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>2</jats:sup>C<jats:sub>2</jats:sub>C<jats:sup>1</jats:sup>, N<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>2</jats:sup>NCS<jats:sup>1</jats:sup>, and N<jats:sup>1</jats:sup>CNN<jats:sup>2</jats:sup>NCSe<jats:sup>1</jats:sup>. The total mean values of τ<jats:sub>4</jats:sub> for respective complexes as it grows in the sequence: 0.056 (Pt(η<jats:sup>3</jats:sup>-O<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>O<jats:sup>2</jats:sup>)(PL)) < 0.091 (Pt(η<jats:sup>3</jats:sup>-Se<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>Se<jats:sup>2</jats:sup>)(PL)) < 0.161 (Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>S<jats:sup>1</jats:sup>)(PL)) < 0.174 (Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>Se<jats:sup>1</jats:sup>)(PL)) < 0.188 (Pt(η<jats:sup>3</jats:sup>-C<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>C<jats:sup>2</jats:sup>)(PL)) < 0.211 (Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>C<jats:sup>1</jats:sup>)(PL)). The distortion of the square-planar geometry increases in the given sequences. The structural data (Pt–L, L–Pt–L) are analyzed and discussed with attention to the distortion of a square-planar geometry about the Pt(<jats:sc>ii</jats:sc>) atoms as well as of <jat
{"title":"Structural aspects of Pt(η3-X1N1X2)(PL) (X1,2 = O, C, or Se) and Pt(η3-N1N2X1)(PL) (X1 = C, S, or Se) derivatives","authors":"Melník Milan, Mikušová Veronika, Mikuš Peter","doi":"10.1515/chem-2023-0204","DOIUrl":"https://doi.org/10.1515/chem-2023-0204","url":null,"abstract":"This article covers 26 Pt(<jats:sc>ii</jats:sc>) complexes of compositions Pt(η<jats:sup>3</jats:sup>-X<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>X<jats:sup>2</jats:sup>)(PL) (X<jats:sup>1,2</jats:sup> = O, C, or Se) and Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>X<jats:sup>1</jats:sup>)(PL) (X<jats:sup>1</jats:sup> = C, S, or Se). These complexes crystallized in two crystal classes: monoclinic (14 examples) and triclinic (12 examples). The heterotridentate ligand with monodentate PL builds up a distorted square-planar geometry around each Pt(<jats:sc>ii</jats:sc>) atom. Each heterotridentate ligand Pt(η<jats:sup>3</jats:sup>-X<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>X<jats:sup>2</jats:sup>)(PL) creates two metallocyclic rings with a common N<jats:sup>1</jats:sup> atom of the O<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>O<jats:sup>2</jats:sup>, O<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>N<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>O<jats:sup>2</jats:sup>, O<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>NN<jats:sup>1</jats:sup>C<jats:sub>3</jats:sub>O<jats:sup>2</jats:sup>, C<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>C<jats:sup>2</jats:sup>, and Se<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>1</jats:sup>NC<jats:sub>2</jats:sub>Se<jats:sup>2</jats:sup> types. In Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>X<jats:sup>1</jats:sup>)(PL) complexes, the tridentate ligand with a common N<jats:sup>2</jats:sup> atom forms the following types of metallocyclic rings: N<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>2</jats:sup>C<jats:sub>2</jats:sub>C<jats:sup>1</jats:sup>, N<jats:sup>1</jats:sup>C<jats:sub>2</jats:sub>N<jats:sup>2</jats:sup>NCS<jats:sup>1</jats:sup>, and N<jats:sup>1</jats:sup>CNN<jats:sup>2</jats:sup>NCSe<jats:sup>1</jats:sup>. The total mean values of τ<jats:sub>4</jats:sub> for respective complexes as it grows in the sequence: 0.056 (Pt(η<jats:sup>3</jats:sup>-O<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>O<jats:sup>2</jats:sup>)(PL)) < 0.091 (Pt(η<jats:sup>3</jats:sup>-Se<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>Se<jats:sup>2</jats:sup>)(PL)) < 0.161 (Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>S<jats:sup>1</jats:sup>)(PL)) < 0.174 (Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>Se<jats:sup>1</jats:sup>)(PL)) < 0.188 (Pt(η<jats:sup>3</jats:sup>-C<jats:sup>1</jats:sup>N<jats:sup>1</jats:sup>C<jats:sup>2</jats:sup>)(PL)) < 0.211 (Pt(η<jats:sup>3</jats:sup>-N<jats:sup>1</jats:sup>N<jats:sup>2</jats:sup>C<jats:sup>1</jats:sup>)(PL)). The distortion of the square-planar geometry increases in the given sequences. The structural data (Pt–L, L–Pt–L) are analyzed and discussed with attention to the distortion of a square-planar geometry about the Pt(<jats:sc>ii</jats:sc>) atoms as well as of <jat","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"8 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140203777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pratibha Pandey, Seema Ramniwas, Meenakshi Verma, Indra Rautela, Fahad Khan, Mohd Asif Shah
Plant-derived bioactive compounds displayed major therapeutic and chemo-preventive roles in the pathogenesis of numerous chronic malignancies such as cancer and enhanced oxidative stress and inflammation. Antioxidants found in food, such as genkwanin, may reduce oxidative stress and the release of cytokines or pathways that promote inflammation. The goal of this work is to summarize the potential for anticancer effects of genkwanin, a methoxyflavone that is present in a variety of plant species. This review examined and analyzed numerous research studies on identifying, isolating, measuring, and analyzing anticancer properties of genkwanin. The mechanisms involved cellular and molecular activities at various levels, including apoptosis induction and cancer cell growth and proliferation inhibition. Preclinical studies have demonstrated genkwanin’s effects and mechanism of action; however, further research is required to investigate its therapeutic potential thoroughly. Additional research is needed to further our understanding of the pharmacodynamic effects of genkwanin. Additional toxicological study is necessary to evaluate the clinical efficacy and safety of genkwanin, which would help scientists to elucidate a potent drug candidate for cancer management.
{"title":"A comprehensive review uncovering the anticancerous potential of genkwanin (plant-derived compound) in several human carcinomas","authors":"Pratibha Pandey, Seema Ramniwas, Meenakshi Verma, Indra Rautela, Fahad Khan, Mohd Asif Shah","doi":"10.1515/chem-2024-0003","DOIUrl":"https://doi.org/10.1515/chem-2024-0003","url":null,"abstract":"Plant-derived bioactive compounds displayed major therapeutic and chemo-preventive roles in the pathogenesis of numerous chronic malignancies such as cancer and enhanced oxidative stress and inflammation. Antioxidants found in food, such as genkwanin, may reduce oxidative stress and the release of cytokines or pathways that promote inflammation. The goal of this work is to summarize the potential for anticancer effects of genkwanin, a methoxyflavone that is present in a variety of plant species. This review examined and analyzed numerous research studies on identifying, isolating, measuring, and analyzing anticancer properties of genkwanin. The mechanisms involved cellular and molecular activities at various levels, including apoptosis induction and cancer cell growth and proliferation inhibition. Preclinical studies have demonstrated genkwanin’s effects and mechanism of action; however, further research is required to investigate its therapeutic potential thoroughly. Additional research is needed to further our understanding of the pharmacodynamic effects of genkwanin. Additional toxicological study is necessary to evaluate the clinical efficacy and safety of genkwanin, which would help scientists to elucidate a potent drug candidate for cancer management.","PeriodicalId":19520,"journal":{"name":"Open Chemistry","volume":"25 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140203716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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