2D QSAR Modelling, Docking, Synthesis and Evaluation of 2-substituted Benzimidazole Derivatives as Anti-breast Cancer Agents

Q2 Pharmacology, Toxicology and Pharmaceutics Current Bioactive Compounds Pub Date : 2023-10-11 DOI:10.2174/0115734072255749230928060834

Remya R.S, Barath R, Ruban R, Jaitharasan V

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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.

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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

背景:癌症是世界范围内死亡的主要原因，预计到2040年全球新病例将达到2840万。尽管在癌症预防、诊断和治疗方面取得了所有进展，但癌症造成的死亡率排在第二位。目的:设计新型2-取代苯并咪唑的QSAR模型。新型衍生物的分子对接研究及其对乳腺癌细胞系mcf7的抗癌活性的合成、表征和评价。方法:设计了10个新型苯并咪唑衍生物。从这10个化合物中，应用计算机工具对ADME性质和毒性进行了分析，并对酪氨酸激酶(PDB ID: 2SRC)进行了分子对接。化合物2AD的dock评分最高，为-9.5 kcal/mol，其次为2bd和2GD (-9.3kcal/mol)。利用在线分子动力学模拟工具CABSflex进行分子动力学模拟研究。选择了6个化合物进行合成。对合成的化合物进行了表征，并采用MTT法对MCF-7细胞株进行了体外药理活性测定。结果:化合物2AD和2GD对MCF-7细胞株有较好的抑制作用，ic50值分别为2.757µg/ml和2.875µg/ml。结论:新型2取代苯并咪唑衍生物是治疗肿瘤的良好先导化合物。这些化合物的优化将提供更多的靶向性抗癌药物。

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来源期刊

Current Bioactive Compounds Pharmacology, 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.