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Synthesis, Anticancer Activity, and In Silico Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer.

التفاصيل البيبلوغرافية
العنوان: Synthesis, Anticancer Activity, and In Silico Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer.
المؤلفون: Abbade Y; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.; Graduate School of Health Sciences, Ankara University, 06110 Ankara, Turkey., Kisla MM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.; Graduate School of Health Sciences, Ankara University, 06110 Ankara, Turkey., Hassan MA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.; Graduate School of Health Sciences, Ankara University, 06110 Ankara, Turkey.; Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Bayero University, P.M.B 3011 Kano, Nigeria., Celik I; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, 38039 Kayseri, Turkey., Dogan TS; Central Laboratory, Molecular Biology and Biotechnology R&D Center, Middle East Technical University, 06800 Ankara, Turkey., Mutlu P; Department of Biotechnology, Biotechnology Institute, Ankara University, 06135 Ankara, Turkey., Ates-Alagoz Z; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.
المصدر: ACS omega [ACS Omega] 2024 Feb 14; Vol. 9 (8), pp. 9547-9563. Date of Electronic Publication: 2024 Feb 14 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101691658 Publication Model: eCollection Cited Medium: Internet ISSN: 2470-1343 (Electronic) Linking ISSN: 24701343 NLM ISO Abbreviation: ACS Omega Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, [2016]-
مستخلص: A series of alkylsulfonyl 1 H -benzo[ d ]imidazole derivatives were synthesized and evaluated for anticancer activity against human breast cancer cells, MCF-7 in vitro . The cytotoxic potential was determined using the xCELLigence real-time cell analysis, and expression levels of genes related to microtubule organization, tumor suppression, apoptosis, cell cycle, and proliferation were examined by quantitative real-time polymerase chain reaction. Molecular docking against Bcl-2 was carried out using AutoDock Vina, while ADME studies were performed to predict the physicochemical and drug-likeness properties of the synthesized compounds. The results revealed that compounds 23 and 27 were the most potent cytotoxic derivatives against MCF-7 cells. Gene expression analysis showed that BCL-2 was the most prominent gene studied. Treatment of MCF-7 cells with compounds 23 and 27 resulted in significant downregulation of the BCL-2 gene, with fold changes of 128 and 256, respectively. Docking analysis predicted a strong interaction between the compounds and the target protein. Interestingly, all of the compounds exhibit a higher binding affinity toward Bcl-2 than the standard drug (compound 27 vina score = -9.6 kcal/mol, vincristine = -6.7 kcal/mol). Molecular dynamics simulations of compounds 23 and 27 showed a permanent stabilization in the binding site of Bcl-2 for 200 ns. Based on Lipinski and Veber's filters, all synthesized compounds displayed drug-like characteristics. These findings suggest that compounds 23 and 27 were the most promising cytotoxic compounds and downregulated the expression of the BCL-2 gene. These derivatives could be further explored as potential candidates for the treatment of breast cancer.
Competing Interests: The authors declare no competing financial interest.
(© 2024 The Authors. Published by American Chemical Society.)
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تواريخ الأحداث: Date Created: 20240304 Latest Revision: 20240305
رمز التحديث: 20240305
مُعرف محوري في PubMed: PMC10905736
DOI: 10.1021/acsomega.3c09411
PMID: 38434899
قاعدة البيانات: MEDLINE
الوصف
تدمد:2470-1343
DOI:10.1021/acsomega.3c09411