Apoptosis inducing properties of 3-biotinylate-6-benzimidazole B-nor-cholesterol analogues

• Published in: Steroids Vol. 169; pp. 108822 - 108828
• Main Authors: Zhu, Zhiling, Liu, Zhiping, Cui, Jianguo, Huang, Yanmin, Chen, Hualong, Wu, Yulan, Huang, Xiaotong, Gan, Chunfang
• Format: Journal Article
• Language: English
• Published: NEW YORK Elsevier Inc 01.05.2021; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; B-nor-cholesterol; Benzimidazole; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Biochemistry & Molecular Biology; Biotin - chemistry; Biotin - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell-cycle; Cholesterol - chemistry; Cholesterol - pharmacology; Drug Screening Assays, Antitumor; Endocrinology & Metabolism; HEK293 Cells; HeLa Cells; Humans; Life Sciences & Biomedicine; Science & Technology; Structure-Activity Relationship; Synthesis; Synthesis; B-nor-cholesterol; Cell-cycle; Benzimidazole; Apoptosis; DESIGN; PROTEIN; P21; VITRO ANTIPROLIFERATIVE EVALUATION; SPONGE; INHIBITORS; DERIVATIVES; HYBRIDS
• ISSN: 0039-128X; 1878-5867; 1878-5867
• DOI: 10.1016/j.steroids.2021.108822

[Display omitted] •Some Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized.•Antiproliferativeactivity and Biological action mechanism of compounds were evaluated.•Compound 6d displays better antiproliferative activity to the test cell lines. In this work, a series of Biotin-substituted B-nor-cholesteryl benzimidazole compounds were synthesized. The antiproliferativeactivities of these compounds were evaluated in vitro using a series of human cancer cell lines, including HeLa (cervical cancer), SKOV3 (ovarian cancer), T-47D (thymus gland cancer), MCF-7 (human breast cancer) and HEK293T (normal renal epithelial) cells. These compounds displayed distinct antiproliferative activities against the currently tested cancer cells. The apoptotic properties induced by compound 6d were further investigated. Our results showed that compound 6d could induce the apoptosis of SKOV3 cells, blocking the cell growth in S-phase. Western blotting analyses revealed that compound 6d can induce cell apoptosis via the mitochondria-dependent pathway.