دورية أكاديمية
Synthesis, Anticancer Activity, and In Silico Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer.
العنوان: | Synthesis, Anticancer Activity, and In Silico Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer. |
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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 |
تدمد: | 2470-1343 |
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DOI: | 10.1021/acsomega.3c09411 |