Weihong Luo, KeXin Zhang, Yali Wang, Miao Ye, Yuqin Zhang, Wei Xu, Lixia Chen, Hua Li
Atractylodes macrocephala Koidz. (A. macrocephala) is a perennial herb of the genus Atractylodes. The rhizome of A. macrocephala (AMR) is its medicinal part. It primarily grows in Southeast Asia and function to invigorate the spleen and qi, drying dampness and removing water. It has long been used for cancer treatment, relieving inflammation, and improving gastrointestinal function, highlighting its remarkable medicinal value. This paper focuses on recent advancements in the traditional uses, phytochemistry, and pharmacology of AMR from 2018 to the present, while exploring its therapeutic and scientific potential. In recent years, more than 120 compounds have been identified in AMR. The primary active components have been identified as sesquiterpenoids, polysaccharides and polyacetylenes. Modern pharmacological studies have demonstrated that AMR has anti-inflammatory, anti-tumor, immunity enhancement, gastrointestinal function improvement, and other pharmacological effects. It is mainly employed in the clinical treatment of tumors and gastrointestinal diseases, showing promising developmental potential. Its mechanism may be related to reducing oxidative stress, inhibiting the expression of inflammatory mediators and factors, and alleviating apoptosis through related signaling pathways. It is hoped that this review can provide a theoretical reference and scientific basis for further systematic research and extensive clinical application of AMR.
白术(Atractylodes macrocephala Koidz.(A.macrocephala)是白术属多年生草本植物。白术的根茎是其药用部分。它主要生长在东南亚,具有健脾益气、燥湿利水的功效。长期以来,它一直被用于治疗癌症、缓解炎症和改善肠胃功能,彰显了其显著的药用价值。本文重点介绍了2018年至今AMR在传统用途、植物化学和药理方面的最新进展,同时探讨其治疗和科研潜力。近年来,AMR 中已鉴定出 120 多种化合物。经鉴定,其主要活性成分为倍半萜、多糖和多炔类化合物。现代药理研究表明,AMR 具有抗炎、抗肿瘤、增强免疫力、改善胃肠功能等药理作用。它主要用于肿瘤和胃肠道疾病的临床治疗,具有广阔的发展前景。其机制可能与减少氧化应激、抑制炎症介质和因子的表达以及通过相关信号通路缓解细胞凋亡有关。希望本综述能为 AMR 的进一步系统研究和广泛临床应用提供理论参考和科学依据。
{"title":"The Rhizome of Atractylodes macrocephala Koidz.: A Comprehensive Review on the Traditional Uses, Phytochemistry and Pharmacology.","authors":"Weihong Luo, KeXin Zhang, Yali Wang, Miao Ye, Yuqin Zhang, Wei Xu, Lixia Chen, Hua Li","doi":"10.1002/cbdv.202401879","DOIUrl":"https://doi.org/10.1002/cbdv.202401879","url":null,"abstract":"<p><p>Atractylodes macrocephala Koidz. (A. macrocephala) is a perennial herb of the genus Atractylodes. The rhizome of A. macrocephala (AMR) is its medicinal part. It primarily grows in Southeast Asia and function to invigorate the spleen and qi, drying dampness and removing water. It has long been used for cancer treatment, relieving inflammation, and improving gastrointestinal function, highlighting its remarkable medicinal value. This paper focuses on recent advancements in the traditional uses, phytochemistry, and pharmacology of AMR from 2018 to the present, while exploring its therapeutic and scientific potential. In recent years, more than 120 compounds have been identified in AMR. The primary active components have been identified as sesquiterpenoids, polysaccharides and polyacetylenes. Modern pharmacological studies have demonstrated that AMR has anti-inflammatory, anti-tumor, immunity enhancement, gastrointestinal function improvement, and other pharmacological effects. It is mainly employed in the clinical treatment of tumors and gastrointestinal diseases, showing promising developmental potential. Its mechanism may be related to reducing oxidative stress, inhibiting the expression of inflammatory mediators and factors, and alleviating apoptosis through related signaling pathways. It is hoped that this review can provide a theoretical reference and scientific basis for further systematic research and extensive clinical application of AMR.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer's disease (AD) is multifactorial, which makes the design of multi-target-directed ligands an attractive strategy for the development of anti-AD drugs. In order to enhance the anti-AD effects and reduce the toxicity, two usnic acid (UA) derivatives (1-2) were designed, synthesized and fully characterized by introducing dimethylamine Schiff base moiety into the toxic "triketone" portion. Ellman's method and molecular docking were used to test the cholinesterase inhibitory activities. Antioxidant activities were studied with Fenton reaction, cyclic voltammetry and C. elegans. The results showed that compared with UA, 1-2 had stronger anti-cholinesterase activities and similar antioxidant activities. Notably, solvent evaporation of 2 and ZnCl2 formed a single crystal, which was revealed to be a Zn(II) complex with UA and tertiary amine as mixed ligands by X-ray diffraction. The hydrolysis of 2 was thus furtherly studied by HPLC. Furthermore, the crystal structure supported the replacement of toxic "triketone" moiety in the chelation process, playing a detoxifying role and at the same time regulating metal homeostasis. In silico prediction also showed low hepatotoxicity and acceptable drug-likeness of 1-2. Overall, this work provided useful insights into multi-target anti-AD candidates with the natural product UA as the lead compound.
阿尔茨海默病(AD)是一种多因素疾病,因此设计多靶点配体是开发抗阿尔茨海默病药物的一种有吸引力的策略。为了提高抗阿尔茨海默病的效果并降低其毒性,我们在有毒的 "三酮 "部分引入了二甲基胺席夫碱基,从而设计、合成并充分表征了两种鸟苷酸(UA)衍生物(1-2)。采用埃尔曼法和分子对接法测试了其胆碱酯酶抑制活性。利用芬顿反应、循环伏安法和 C. elegans 对抗氧化活性进行了研究。结果表明,与 UA 相比,1-2 具有更强的抗胆碱酯酶活性和相似的抗氧化活性。值得注意的是,将 2 和 ZnCl2 溶剂蒸发后形成了单晶体,通过 X 射线衍射发现它是以 UA 和叔胺为混合配体的 Zn(II)配合物。因此,通过高效液相色谱法进一步研究了 2 的水解过程。此外,晶体结构支持在螯合过程中取代有毒的 "三酮 "分子,在发挥解毒作用的同时调节金属的平衡。硅学预测还显示,1-2 的肝毒性较低,药物亲和性也可以接受。总之,这项工作为以天然产物 UA 为先导化合物的多靶点抗逆转录酶候选化合物提供了有益的见解。
{"title":"Usnic Acid Derivatives as Multi-Target Anti-Alzheimer's Disease Agents: Design, Synthesis, X-Ray Single Crystal Structure of Zn(II) Complex and Biological Activities.","authors":"Lihua Zhao, Bingbing Li, Lin Zheng","doi":"10.1002/cbdv.202401548","DOIUrl":"https://doi.org/10.1002/cbdv.202401548","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is multifactorial, which makes the design of multi-target-directed ligands an attractive strategy for the development of anti-AD drugs. In order to enhance the anti-AD effects and reduce the toxicity, two usnic acid (UA) derivatives (1-2) were designed, synthesized and fully characterized by introducing dimethylamine Schiff base moiety into the toxic \"triketone\" portion. Ellman's method and molecular docking were used to test the cholinesterase inhibitory activities. Antioxidant activities were studied with Fenton reaction, cyclic voltammetry and C. elegans. The results showed that compared with UA, 1-2 had stronger anti-cholinesterase activities and similar antioxidant activities. Notably, solvent evaporation of 2 and ZnCl2 formed a single crystal, which was revealed to be a Zn(II) complex with UA and tertiary amine as mixed ligands by X-ray diffraction. The hydrolysis of 2 was thus furtherly studied by HPLC. Furthermore, the crystal structure supported the replacement of toxic \"triketone\" moiety in the chelation process, playing a detoxifying role and at the same time regulating metal homeostasis. In silico prediction also showed low hepatotoxicity and acceptable drug-likeness of 1-2. Overall, this work provided useful insights into multi-target anti-AD candidates with the natural product UA as the lead compound.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mashael A Alghamdi, Faizul Azam, Md Sarfaraj Hussain, Mohamed A M Ali, Md Jamir Anwar, Danish Mahmood
Hygrophila auriculata (K. Schum) Heine is known to treat various common aliment e.g. rheumatoid arthritis, kidney infections, jaundice, edema, and gout. This study aims to isolate bioactive components from the methanolic extract, assess their anti-inflammatory effects, and investigate their interactions with drug targets through docking and molecular dynamics simulations. Methanolic extract of H. auriculata furnished stigmast-5-en-3-ol-β-D-glucopyranoside (HA-06) which was characterized by using IR, NMR and mass spectral data. HA-06 alleviated carrageenan-induced inflammation in rats, while the methanolic extract of H. auriculata produced comparable results. The findings were similar to those of the positive control, indomethacin. The chemical structure of HA-06 was optimized using DFT at the B3LYP level and subsequently used for molecular docking against anti-inflammatory drug targets. HA-06 exhibited strong affinity towards phospholipase A2 and glucocorticoid receptor exhibiting binding energies of -11.25 kcal/mol and -11.07 kcal/mol, respectively.Molecular dynamics simulation was used to assess the dynamical stability of these two complexes and their native co-crystallized ligands. Principal component analysis, radius of gyration, free energy landscapes, solvent-accessible-surface-area, and root-mean square deviation/fluctuation all indicated stable interactions. Therefore, HA-06 could be a promising candidate for development into an effective therapy against inflammatory diseases targeting phospholipase A2 and glucocorticoid receptor.
{"title":"Isolation, Characterization, and Anti-Inflammatory Effects of β-Sitosterol-β-D-Glucoside from Hygrophila auriculata: Experimental Validation, Molecular Docking, and Molecular Dynamics Simulations.","authors":"Mashael A Alghamdi, Faizul Azam, Md Sarfaraj Hussain, Mohamed A M Ali, Md Jamir Anwar, Danish Mahmood","doi":"10.1002/cbdv.202401927","DOIUrl":"https://doi.org/10.1002/cbdv.202401927","url":null,"abstract":"<p><p>Hygrophila auriculata (K. Schum) Heine is known to treat various common aliment e.g. rheumatoid arthritis, kidney infections, jaundice, edema, and gout. This study aims to isolate bioactive components from the methanolic extract, assess their anti-inflammatory effects, and investigate their interactions with drug targets through docking and molecular dynamics simulations. Methanolic extract of H. auriculata furnished stigmast-5-en-3-ol-β-D-glucopyranoside (HA-06) which was characterized by using IR, NMR and mass spectral data. HA-06 alleviated carrageenan-induced inflammation in rats, while the methanolic extract of H. auriculata produced comparable results. The findings were similar to those of the positive control, indomethacin. The chemical structure of HA-06 was optimized using DFT at the B3LYP level and subsequently used for molecular docking against anti-inflammatory drug targets. HA-06 exhibited strong affinity towards phospholipase A2 and glucocorticoid receptor exhibiting binding energies of -11.25 kcal/mol and -11.07 kcal/mol, respectively.Molecular dynamics simulation was used to assess the dynamical stability of these two complexes and their native co-crystallized ligands. Principal component analysis, radius of gyration, free energy landscapes, solvent-accessible-surface-area, and root-mean square deviation/fluctuation all indicated stable interactions. Therefore, HA-06 could be a promising candidate for development into an effective therapy against inflammatory diseases targeting phospholipase A2 and glucocorticoid receptor.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad G Al-Thiabat, Mohit Agrawal, Kantrol Kumar Sahu, Maram B Alhawarri, Katreen Banisalman, Ghazi A Al Jabal, Haya Saleh Elqaderi
This study explores the therapeutic potential of three proaporphine alkaloids-cissamaline, cissamanine, and cissamdine, which were recently isolated from Cissampelos capensis L.f., against Parkinson's disease (PD). Using computational techniques, we investigated their efficacy as inhibitors of a key protein in PD. ADMET analysis demonstrated that these alkaloids conform to the Lipinski, Pfizer, Golden Triangle, and GSK rules, indicating favorable safety, oral bioavailability, and a high probability of passing the human intestinal and blood-brain barriers. They were neither substrates nor inhibitors of any CYP enzymes tested, indicating minimal metabolic interference and an enhanced safety profile. Molecular docking studies revealed strong binding energies with MAO-B, PD's target. MD simulations supported these findings, showing stable interactions with MAO-B, while Density Functional Theory (DFT) calculations highlighted the electrophilic nature of cissamanine, enhancing its potential as an effective inhibitor. These results advocate further in vitro and in vivo studies to evaluate their potential as PD therapeutics.
{"title":"Potential MAO-B Inhibitors from Cissampelos capensis L.f.: ADMET, Molecular Docking, Dynamics, and DFT Insights.","authors":"Mohammad G Al-Thiabat, Mohit Agrawal, Kantrol Kumar Sahu, Maram B Alhawarri, Katreen Banisalman, Ghazi A Al Jabal, Haya Saleh Elqaderi","doi":"10.1002/cbdv.202402351","DOIUrl":"https://doi.org/10.1002/cbdv.202402351","url":null,"abstract":"<p><p>This study explores the therapeutic potential of three proaporphine alkaloids-cissamaline, cissamanine, and cissamdine, which were recently isolated from Cissampelos capensis L.f., against Parkinson's disease (PD). Using computational techniques, we investigated their efficacy as inhibitors of a key protein in PD. ADMET analysis demonstrated that these alkaloids conform to the Lipinski, Pfizer, Golden Triangle, and GSK rules, indicating favorable safety, oral bioavailability, and a high probability of passing the human intestinal and blood-brain barriers. They were neither substrates nor inhibitors of any CYP enzymes tested, indicating minimal metabolic interference and an enhanced safety profile. Molecular docking studies revealed strong binding energies with MAO-B, PD's target. MD simulations supported these findings, showing stable interactions with MAO-B, while Density Functional Theory (DFT) calculations highlighted the electrophilic nature of cissamanine, enhancing its potential as an effective inhibitor. These results advocate further in vitro and in vivo studies to evaluate their potential as PD therapeutics.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Four new tremulane sesquiterpenes, named phaeosphaerienols A-D (1-4), and two new pyroglutamate-containing dipeptides, named phaeosphaeratides A-B (5-6), were isolated from the mangrove endophytic fungus Phaeosphaeriopsis sp. P11, together with a new 2-furancarboxylic acid derivative (7). Structurally, pheaosphaerienols A-C (1-3) are rare tremulanes containing a 1,10-epoxide moiety. The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and Marfey's derivatization method. All the isolates were evaluated for their cytotoxic, antibacterial, and DPPH free radical scavenging effects. However, none of the compounds exhibited obvious activities.
{"title":"Four Tremulanes and Two Pyroglutamate-Containing Dipeptides from the Mangrove Endophytic Fungus Phaeosphaeriopsis sp. P11.","authors":"Yong-Cong Yuan, Jun-Sheng Li, Li Shen, Jun Wu","doi":"10.1002/cbdv.202402556","DOIUrl":"https://doi.org/10.1002/cbdv.202402556","url":null,"abstract":"<p><p>Four new tremulane sesquiterpenes, named phaeosphaerienols A-D (1-4), and two new pyroglutamate-containing dipeptides, named phaeosphaeratides A-B (5-6), were isolated from the mangrove endophytic fungus Phaeosphaeriopsis sp. P11, together with a new 2-furancarboxylic acid derivative (7). Structurally, pheaosphaerienols A-C (1-3) are rare tremulanes containing a 1,10-epoxide moiety. The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and Marfey's derivatization method. All the isolates were evaluated for their cytotoxic, antibacterial, and DPPH free radical scavenging effects. However, none of the compounds exhibited obvious activities.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matheus Fernandes Alves, Albert Katchborian Neto, Rosana Casoti, Fernanda Brito Leite, Ana Chagas de Paula Ladvocat, Danielle Ferreira Dias, Marisi Gomes Soares, Tiago Arruda Sanchez, Daniela Aparecida Chagas de Paula
Ocotea is an important genus of Lauraceae plant family that comprises over 400 species, many of which pose challenges in taxonomic differentiation due to their complex botanical characteristics. Chemosystematics, and more recently, chemophenetics, have emerged as valuable tools to address these challenges based on their natural products (NPs) composition. O. diospyrifolia (Meisn.) Mez is a poorly studied species with known pharmacological potential. Here, we applied ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS) allied to a curated in-house database with all previous isolated NPs from the Ocotea genus (OcoteaDB), gas phase fragmentations reactions, and biosynthesis. The strategy resulted in compounds annotated in confidence levels 2 (n=27), 3 (n=231), and 4 (n=21) according to the Metabolomics Standards Initiative (MSI). Additional annotations based on fragmentation proposals (n=16) were also included. The study revealed that O. diospyrifolia is a great alkaloid producer, even though different lignoids, which also comes from the shikimate pathway, were annotated. Additionally, the flavonoid profile predominantly consists of flavonol glycosides, complementing prior reports. This study provides the first comprehensive chemical profile of O. diospyrifolia leaves, which corroborates the chemotaxonomy of the species, and also contributes to further characterization studies, as the UHPLC-HRMS data is publicly available.
{"title":"High-Resolution Tandem Mass Spectrometry for Metabolic Profiling of Ocotea diospyrifolia (Meisn.) Mez Leaves.","authors":"Matheus Fernandes Alves, Albert Katchborian Neto, Rosana Casoti, Fernanda Brito Leite, Ana Chagas de Paula Ladvocat, Danielle Ferreira Dias, Marisi Gomes Soares, Tiago Arruda Sanchez, Daniela Aparecida Chagas de Paula","doi":"10.1002/cbdv.202402227","DOIUrl":"https://doi.org/10.1002/cbdv.202402227","url":null,"abstract":"<p><p>Ocotea is an important genus of Lauraceae plant family that comprises over 400 species, many of which pose challenges in taxonomic differentiation due to their complex botanical characteristics. Chemosystematics, and more recently, chemophenetics, have emerged as valuable tools to address these challenges based on their natural products (NPs) composition. O. diospyrifolia (Meisn.) Mez is a poorly studied species with known pharmacological potential. Here, we applied ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS) allied to a curated in-house database with all previous isolated NPs from the Ocotea genus (OcoteaDB), gas phase fragmentations reactions, and biosynthesis. The strategy resulted in compounds annotated in confidence levels 2 (n=27), 3 (n=231), and 4 (n=21) according to the Metabolomics Standards Initiative (MSI). Additional annotations based on fragmentation proposals (n=16) were also included. The study revealed that O. diospyrifolia is a great alkaloid producer, even though different lignoids, which also comes from the shikimate pathway, were annotated. Additionally, the flavonoid profile predominantly consists of flavonol glycosides, complementing prior reports. This study provides the first comprehensive chemical profile of O. diospyrifolia leaves, which corroborates the chemotaxonomy of the species, and also contributes to further characterization studies, as the UHPLC-HRMS data is publicly available.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Sajid, Hina Siddiqui, Muhammad Atif, Ruby Sharif, Humaira Zafar, Michael D Threadgill, M Iqbal Choudhary
Aromatase inhibitors are among the most effective treatment of the breast cancer. Aromatase catalyzes estrogen biosynthesis, which is a long-term cause of breast cancer. Current study describes the synthesis, purification of 26 new fluorinated and non-fluorinated thiourea derivatives of desloratadine (5), and their aromatase inhibition activity, cytotoxicity against cancer cell line (MDA-MB-231). Compounds 7v and 7l exhibited a significant anti-aromatase activity, while compounds 7a, 7g-h, 7m and 7u were also significant active against MDA-MB-231 cell line. Furthermore, the molecular docking studies revealed that active compounds form key interactions with the crucial amino acid of aromatase active site including TRP224, LEU477, CYS437, ALA438, MET374, ARG115, ILE305, and PHE221, which are responsible for the binding interaction of aromatase. All analogues were new, except 7b and 7k and also lacked cytotoxicity BJ human fibroblasts, with the exception of 5 and 7x. This selectivity makes this series particularly interesting for further studies.
{"title":"Synthesis, Aromatase Inhibition, Cytotoxicity and Molecular Docking Studies of New Fluorinated and Non-fluorinated Thiourea Derivatives of Desloratadine.","authors":"Muhammad Sajid, Hina Siddiqui, Muhammad Atif, Ruby Sharif, Humaira Zafar, Michael D Threadgill, M Iqbal Choudhary","doi":"10.1002/cbdv.202402117","DOIUrl":"https://doi.org/10.1002/cbdv.202402117","url":null,"abstract":"<p><p>Aromatase inhibitors are among the most effective treatment of the breast cancer. Aromatase catalyzes estrogen biosynthesis, which is a long-term cause of breast cancer. Current study describes the synthesis, purification of 26 new fluorinated and non-fluorinated thiourea derivatives of desloratadine (5), and their aromatase inhibition activity, cytotoxicity against cancer cell line (MDA-MB-231). Compounds 7v and 7l exhibited a significant anti-aromatase activity, while compounds 7a, 7g-h, 7m and 7u were also significant active against MDA-MB-231 cell line. Furthermore, the molecular docking studies revealed that active compounds form key interactions with the crucial amino acid of aromatase active site including TRP224, LEU477, CYS437, ALA438, MET374, ARG115, ILE305, and PHE221, which are responsible for the binding interaction of aromatase. All analogues were new, except 7b and 7k and also lacked cytotoxicity BJ human fibroblasts, with the exception of 5 and 7x. This selectivity makes this series particularly interesting for further studies.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jovana S Marjanović, Nevena Petrović, Marijana Kosanić, Jelena Košarić, Ana Mirić, Nevena Milivojević, Marina D Kostić, Vera M Divac
Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine-derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p-nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT-116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC-5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT-DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.
在有机支架中引入吲哚类药物结构可以产生有趣的药理特性,受此启发,我们合成了一系列新型色胺衍生希夫碱。色胺被用作吲哚模式的来源,同时也是生物胺的一个例子,通过化学转化可以得到具有显著生物活性的化合物。针对一系列细菌和真菌菌株的抗菌活性以及细胞毒性活性的研究结果表明,在结构上结合了色胺和对硝基芳基模式的希夫碱 TSB4 在低浓度下比标准药物氟康唑具有更好的抗真菌活性,而由色胺和喹啉分子组成分子支架的化合物 TSB6 对 HCT-116 细胞系具有一定的细胞毒性作用,对健康的成纤维细胞 MRC-5 具有很强的选择性。为了更好地了解这两种化合物的药代动力学并确定其与 DNA 分子的结合模式,我们对这两种化合物进行了额外的 ADME 分析和 DNA 相互作用分析。结果表明,所研究的化合物与 CT-DNA 有很强的结合力,而 ADME 筛选表明,所选化合物具有适合口服生物利用度和药物亲和性的理化特性。
{"title":"Tryptamine-Derived Schiff Bases: Potent Antimicrobial Agents and Evaluation of Cytotoxicity, ADME and DNA Binding Properties.","authors":"Jovana S Marjanović, Nevena Petrović, Marijana Kosanić, Jelena Košarić, Ana Mirić, Nevena Milivojević, Marina D Kostić, Vera M Divac","doi":"10.1002/cbdv.202401699","DOIUrl":"https://doi.org/10.1002/cbdv.202401699","url":null,"abstract":"<p><p>Inspired by the fact that the introduction of indole pharmacophore in organic scaffolds could enable interesting pharmacological properties, the series of novel tryptamine-derived Schiff bases was synthetized. Tryptamine was used as a source of indole pattern, as well as an example of biogenic amines which chemical transformations lead to the compounds with prominent biological activities. The obtained results for antimicrobial activity against a range of bacterial and fungal strains and cytotoxic activities have revealed that Schiff base TSB4 combining the tryptamine and p-nitro aryl patterns in the structure showed better antifungal activity at low concentrations than standard drug Fluconazole, while compound TSB6 with molecular scaffold composed from tryptamine and quinoline moieties showed certain cytotoxic effect on HCT-116 cell line with a strongly expressed selectivity about healthy fibroblast cells, MRC-5. For these two selected compounds, additional ADME analysis and DNA interactions were performed. to obtain better insight into their pharmacokinetics and determination of binding mode for DNA molecules. As results suggested, strong binding of examined compounds to CT-DNA was observed, while the ADME screening showed that selected compounds possess suitable physicochemical properties for oral bioavailability and druglikeness.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rajarshi Nath, Swarup Manna, Sambo Panda, Arindam Maity, Krishnalekha Bandyopadhyay, Arijit Das, Shah Alam Alam Khan, Biplab Debnath, Md Jawaid Akhtar
The toxicity associated with synthetic drugs used for treating various diseases is common. This led to a growing interest in searching and incorporating natural functional core structures such as flavonoid and their derivatives via chemical modifications to overcome the toxicity problems and enhance their biological spectrum. Natural core structures such as flavonoids are accepted due to their safety to the environment and owing to their varieties of biological activities such as anti-Alzheimer, antimicrobial, anticancer, anti-inflammatory, antidiabetics, and antiviral properties. Based on their chemical structure, flavonoids are classified into various classes such as flavone, flavanol, flavanone, isoflavone, and Anthocyanin, etc. The present review focuses on the potential role of the flavonoid ring-containing derivatives, highlighting their ability to prevent and treat non-communicable diseases such as diabetes, Alzheimer's, and cancer. The pharmacological activities of the flavonoid's derivatives are mainly attributed to their antioxidant effects against free radicals, and reactive oxygen species as well as their ability to act as enzymes inhibitors. The review covers the synthetic strategies of flavonoid derivatives, structure activity relationship (SAR), and in silico studies to improve the efficacy of these compounds. The SAR, molecular docking analysis will enable medicinal chemists to search further, develop potent and newer therapeutic agents.
用于治疗各种疾病的合成药物普遍存在毒性问题。因此,人们越来越关注通过化学修饰来寻找和加入天然功能核心结构,如类黄酮及其衍生物,以克服毒性问题并增强其生物活性。黄酮类化合物等天然核心结构因其对环境的安全性和多种生物活性(如抗老年痴呆、抗菌、抗癌、抗炎、抗糖尿病和抗病毒特性)而被广泛接受。根据其化学结构,类黄酮可分为黄酮、黄烷醇、黄烷酮、异黄酮和花青素等不同类别。本综述重点关注含黄酮环衍生物的潜在作用,强调它们在预防和治疗糖尿病、老年痴呆症和癌症等非传染性疾病方面的能力。黄酮类衍生物的药理活性主要归因于它们对自由基和活性氧的抗氧化作用,以及作为酶抑制剂的能力。本综述涵盖了黄酮类衍生物的合成策略、结构活性关系(SAR)以及旨在提高这些化合物功效的硅学研究。通过 SAR 和分子对接分析,药物化学家可以进一步寻找、开发更有效、更新的治疗药物。
{"title":"Flavonoid Based Development of Synthetic Drugs: Chemistry and Biological Activities.","authors":"Rajarshi Nath, Swarup Manna, Sambo Panda, Arindam Maity, Krishnalekha Bandyopadhyay, Arijit Das, Shah Alam Alam Khan, Biplab Debnath, Md Jawaid Akhtar","doi":"10.1002/cbdv.202401899","DOIUrl":"https://doi.org/10.1002/cbdv.202401899","url":null,"abstract":"<p><p>The toxicity associated with synthetic drugs used for treating various diseases is common. This led to a growing interest in searching and incorporating natural functional core structures such as flavonoid and their derivatives via chemical modifications to overcome the toxicity problems and enhance their biological spectrum. Natural core structures such as flavonoids are accepted due to their safety to the environment and owing to their varieties of biological activities such as anti-Alzheimer, antimicrobial, anticancer, anti-inflammatory, antidiabetics, and antiviral properties. Based on their chemical structure, flavonoids are classified into various classes such as flavone, flavanol, flavanone, isoflavone, and Anthocyanin, etc. The present review focuses on the potential role of the flavonoid ring-containing derivatives, highlighting their ability to prevent and treat non-communicable diseases such as diabetes, Alzheimer's, and cancer. The pharmacological activities of the flavonoid's derivatives are mainly attributed to their antioxidant effects against free radicals, and reactive oxygen species as well as their ability to act as enzymes inhibitors. The review covers the synthetic strategies of flavonoid derivatives, structure activity relationship (SAR), and in silico studies to improve the efficacy of these compounds. The SAR, molecular docking analysis will enable medicinal chemists to search further, develop potent and newer therapeutic agents.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}