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Published on: February 9, 2021
Design and synthesis of Tetrahydroindeno[4,5-c]chromen-4(3H)-one derivatives as antiproliferative agents for prostate
Hui-Yu Chan1, Pin-Shuo Huang2, Pei-Fang Chiu2
1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan; Department of Pharmacy, Changhua Christian Hospital, Changhua 500, Taiwan.
Abstract:
Abiraterone, a CYP17A1 inhibitor, is approved by the FDA for castration-resistance prostate cancer. To mimic the structure of abiraterone, we designed and synthesized nine tetrahydroindeno[4,5-c]chromen-4(3H)-one derivatives with pyridine congeners at C-1 position. Notably, 13c and 14c exhibited the GI50 of 10 nM against PC-3 cells compared to 21.4 μM for abiraterone. The docking studies further revealed that 14c shares a similar binding mode with abiraterone at the CYP17A1 active site.
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