Novel thienopyridine derivatives as specific anti-hepatocellular carcinoma (HCC) agents: Synthesis, preliminary structure–activity relationships, and in vitro biological evaluation

• Published in: Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (21), p.6282-6285
• Main Authors: Zeng, Xiu-Xiu, Zheng, Ren-Lin, Zhou, Tian, He, Hai-Yun, Liu, Ji-Yan, Zheng, Yu, Tong, Ai-Ping, Xiang, Ming-Li, Song, Xiang-Rong, Yang, Sheng-Yong, Yu, Luo-Ting, Wei, Yu-Quan, Zhao, Ying-Lan, Yang, Li
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - pharmacology; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Carcinoma, Hepatocellular - drug therapy; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclization; DNA - biosynthesis; DNA - genetics; Doxorubicin - pharmacology; Flow Cytometry; G 0/G 1 cell cycle arrest; G1 Phase - drug effects; General aspects; HCC-specific anticancer activity; Hepatocellular carcinoma (HCC); Humans; Liver Neoplasms - drug therapy; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacology. Drug treatments; Resting Phase, Cell Cycle - drug effects; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Structure–activity relationships (SARs); Thienopyridine; Thienopyridines - chemical synthesis; Thienopyridines - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.08.088

Among 17 analogs of 1a, the most potent analog 1g possesses hepatocellular carcinoma (HCC)-specific anticancer activity. It was inactive toward a panel of five different types of human cancer cell lines. Novel thienopyridine derivatives 1b– 1r were synthesized, based on a hit compound 1a that was found in a previous cell-based screening of anticancer drugs. Compounds 1a– 1r have the following features: (1) their anticancer activity in vitro was first reported by our group. (2) The most potent analog 1g possesses hepatocellular carcinoma (HCC)-specific anticancer activity. It can specifically inhibit the proliferation of the human hepatoma HepG2 cells with an IC 50 value of 0.016 μM (compared with doxorubicin as a positive control, whose IC 50 was 0.37 μM). It is inactive toward a panel of five different types of human cancer cell lines. (3) Compound 1g remarkably induces G 0/G 1 arrest and apoptosis in HepG2 cells in vitro at low micromolar concentrations. These results, especially the HCC-specific anticancer activity of 1g, suggest their potential in targeted chemotherapy for HCC.