Development of thieno[3',2':5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as the estrogen receptor ligands: synthesis, characterization and biological activity.
Estrogen receptors (ERs) are members of a superfamily of ligand-modulated nuclear receptors, which have been associated with an increased risk of cardiovascular diseases and breast cancer. Based on molecular docking studies, 1,4-dihydrothieno[3',2':5,6]thiopyrano[4,3-c]pyrazole-3-carboxamide derivatives as estrogen receptor inhibitors with a new scaffold , have been synthesized and tested for the antitumor activity on the ER expressing (ER dependent) human MCF-7 breast cancer cell line. According to the biological activity evaluation, compound 6a demonstrated the most potent antiproliferative activity (relative inhibitory rate: 100%). Several of these compounds exhibited moderate antitumor activity and worthy of further modification to obtain more potent anticancer candidate drugs.
Xin
X
Wang
Rui
R
Sun
Yushu
Y
Huang
Yisi
Y
Yan
Miaomiao
M
Gao
Dan-Ni
DN
Wang
Diwa
D
Koirala
Da-Wei
DW
Li
Key Laboratory of Structure- Based Drug Design & Discovery, Ministry of Education, China, Shenyang Pharmaceutical University, Shenyang 110016, China. chunhu@syphu.edu.cn.
Chun
C
Hu
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008024:Ligands; D011720:Pyrazoles