Investigation of 2-phenylimidazo[1,2-a]quinolines as potential antiproliferative agents.

Abstract

Background: It has been demonstrated that the lead compound 2-phenylimidazo[1,2-a]quinoline 1a selectively inhibits CYP1 enzymes. Additionally, CYP1 inhibition has been linked to inducing antiproliferative effects in various breast cancer cell lines as well as relieving drugresistance caused by CYP1 upregulation. Materials & methods: Herein, 54 novel analogsof 2-phenylimidazo[1,2-a]quinoline 1a have beensynthesized with varied substitution on the phenyl and imidazole rings. Antiproliferative testing was conducted using 3H thymidine uptake assays. Results: 2-Phenylimidazo[1,2-a]quinoline 1a and phenyl-substituted analogs 1c (3-OMe), 1n (2,3-napthalene) displayed excellent anti-proliferative activities, demonstrating theirpotency against cancer cell lines for the first time. Molecular modeling suggested that 1c and 1n bind similarly to 1a in the CYP1 binding site.