Synthesis and biological evaluation of novel pyrimidine–benzimidazol hybrids as potential anticancer agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 16; pp. 3877 - 3881
• Main Authors: Shao, Kun-Peng, Zhang, Xu-Yao, Chen, Peng-Ju, Xue, Deng-Qi, He, Peng, Ma, Li-Ying, Zheng, Jia-Xin, Zhang, Qiu-Rong, Liu, Hong-Min
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-08-2014
• Subjects: Anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Benzimidazole; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Cell Cycle - drug effects; Cell cycle arrest; Cell Death - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; MCF-7 Cells; Molecular Structure; Pyrimidine; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Cell cycle arrest; Anticancer; Benzimidazole; Pyrimidine; Apoptosis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.06.050

Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55μM and 1.06 to 12.89μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.
A series of pyrimidine–benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a–b and 6a–b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55μM and 1.06 to 12.89μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.