{"title":"2-取代苯并咪唑类抗乳腺癌药物的二维QSAR建模、对接、合成及评价","authors":"Remya R.S, Barath R, Ruban R, Jaitharasan V","doi":"10.2174/0115734072255749230928060834","DOIUrl":null,"url":null,"abstract":"Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place. Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7. Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying insilico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay. Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line withIC50 values of 2.757 µg/ml and 2.875 µg/ml respectively. Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.","PeriodicalId":10772,"journal":{"name":"Current Bioactive Compounds","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"2D QSAR Modelling, Docking, Synthesis and Evaluation of 2-substituted Benzimidazole Derivatives as Anti-breast Cancer Agents\",\"authors\":\"Remya R.S, Barath R, Ruban R, Jaitharasan V\",\"doi\":\"10.2174/0115734072255749230928060834\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place. Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7. Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying insilico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay. Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line withIC50 values of 2.757 µg/ml and 2.875 µg/ml respectively. Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.\",\"PeriodicalId\":10772,\"journal\":{\"name\":\"Current Bioactive Compounds\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Bioactive Compounds\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0115734072255749230928060834\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Bioactive Compounds","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115734072255749230928060834","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
2D QSAR Modelling, Docking, Synthesis and Evaluation of 2-substituted Benzimidazole Derivatives as Anti-breast Cancer Agents
Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place. Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7. Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying insilico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay. Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line withIC50 values of 2.757 µg/ml and 2.875 µg/ml respectively. Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.
Current Bioactive CompoundsPharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.90
自引率
0.00%
发文量
112
期刊介绍:
The journal aims to provide comprehensive review articles on new bioactive compounds with proven activities in various biological screenings and pharmacological models with a special emphasis on stereoeselective synthesis. The aim is to provide a valuable information source of bioactive compounds synthesized or isolated, which can be used for further development of pharmaceuticals by industry and academia. The journal should prove to be essential reading for pharmacologists, natural product chemists and medicinal chemists who wish to be kept informed and up-to-date with the most important developments on new bioactive compounds of natural or synthetic origin, including their stereoeselective synthesis.