Novel thienopyridine derivatives as specific anti-hepatocellular carcinoma (HCC) agents: synthesis, preliminary structure-activity relationships, and in vitro biological evaluation.
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 0.016μM (compared with doxorubicin as a positive control, whose IC(50) was 0.37μM). 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.
Zeng
Xiu-Xiu
XX
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicinal School, Sichuan University, Chengdu 610041, Sichuan, China.
Zheng
Ren-Lin
RL
Zhou
Tian
T
He
Hai-Yun
HY
Liu
Ji-Yan
JY
Zheng
Yu
Y
Tong
Ai-Ping
AP
Xiang
Ming-Li
ML
Song
Xiang-Rong
XR
Yang
Sheng-Yong
SY
Yu
Luo-Ting
LT
Wei
Yu-Quan
YQ
Zhao
Ying-Lan
YL
Yang
Li
L
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D058924:Thienopyridines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D058924:Thienopyridines; D004317:Doxorubicin; D004247:DNA