Synthesis and Evaluation of 3,5-Disubstituted-1,2,4-Oxadiazolyl Benzamides as Potential Anti-Breast Cancer Agents: In Vitro and In Silico Studies.

Autor: Asad M; Department of Chemistry, TCG Life Science, Kolakata, 700091, WB, India., Karim S; Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia., Sanobar; Department of Chemistry, Govt. Raza P.G. College, (M.J.P Rohil Khand University, Bareilly), Rampur, 244901, UP, India., Faheem Khan M; Department of Biotechnology, Era's Lucknow Medical College, Era University, Lucknow, 226003, UP, India., Ahmad Ansari W; Department of Biotechnology, Era's Lucknow Medical College, Era University, Lucknow, 226003, UP, India., Al Said Y; Department of Neurosciences, King Faisal Specialist Hospital & Research Centre, Jeddah, 21556, Saudi Arabia., Imran Khan M; Research Centre, King Faisal Specialist Hospital and Research Centre, Jeddah, 21499, Saudi Arabia.; Department of Biochemistry and Molecular Medicine, College of Medicine, Al-Faisal University, Riyadh, 11533, Saudi Arabia., Saquib M; Department of Chemistry, University of Allahabad, Prayagraj (Allahabad), 211002, UP, India.; Department of Chemistry, G. R. P. B. Degree College, P. R. S. University, Prayagraj (Allahabad), 211010, UP, India., Kamil Hussain M; Department of Chemistry, Govt. Raza P.G. College, (M.J.P Rohil Khand University, Bareilly), Rampur, 244901, UP, India.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Nov 04, pp. e202402020. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1002/cbdv.202402020
Abstrakt: Herein, the synthesis, anti-cancer evaluation, and in silico studies of a series of 1,2,4-oxadiazole compounds (8-15) are disclosed. The synthesized molecules were tested in vitro for anti-cancer activity against MCF-7, MDA-MB-231, HeLa, Ishikawa cell lines and human embryonic kidney (HEK-293) cell lines. Among the synthesized compounds, 9 and 15 exhibited significant cytotoxicity, with IC 50 values of 7.82 μM and 6.02 μM, respectively, against MCF-7 cell line, better than that of anti-breast cancer drug, tamoxifen (IC 50 =11.92 μM), used as control. Significantly, both 9 and 15 exhibited very low toxicity (IC 50 >20 μM) against normal HEK-293 cells. This suggests them as potentially effective anti-cancer lead molecules. The in vitro anti-cancer data was supported by in silico studies which also identified compounds 9 and 15 as potent inhibitors of the 17β-hydroxysteroid dehydrogenase1 (17β-HSD1) proteins, demonstrating strong interactions and stability The atom-based QSAR model exhibited high accuracy, significant regression, and predictive reliability, aiding in understanding and optimizing biological activity. The drug-likeness study of compounds 9 and 15 indicated favorable pharmacokinetics, with in silico toxicity predictions showing compound 15 to be non-toxic. These findings suggest compounds 9 and 15 as potential lead molecules against breast cancer.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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