Design and evaluation of novel oxadiazole derivatives as potential prostate cancer agents

• Published in: Bioorganic & medicinal chemistry letters 2016-06, Vol.26 (12), p.2847-2851
• Main Authors: Mochona, Bereket, Qi, Xin, Euynni, Suresh, Sikazwi, Donald, Mateeva, Nelly, Soliman, Karam F.
• Format: Article
• Language: English
• Subjects: 1,3,4-Oxadiazole; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Azoles; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Male; Models, Molecular; Molecular Structure; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.04.058

[Display omitted] Various 1,3,4-oxadiazole derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cell lines. Most of the compounds showed promising activity. Among them, compounds 2d (IC50=0.22 and 1.3μM) and 2a (IC50=8.34 and 2,5μM) have shown significant activities on PC-3 and LNCaP cell lines respectively. To investigate the mechanism of cell death we performed cell apoptosis staining and cell cycle arrest assay on more sensitive PC-3 cell lines on 2d. The results demonstrated that 2d induced apoptosis and shifted the cells to the sub G0/G1 and S phase. Our study evidently identified the potency of compound 2d as potential anti-prostate cancer agent.