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Synthesis and Antitrypanosomal Activity of Novel 2-Nitroimidazole-3,5-Disubstituted Isoxazole Derivatives with Diaryl Ether and Thioether Substituents

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide In this study, we synthesized 17 novel 2-nitroimidazole-3,5-disubstituted isoxazole analogs of benznidazole with diaryl ether and thioether substituents and evaluated their antitrypanosomal activity and cytotoxicity. Compounds 6a – q were obtained in moderate-to-good yields (29–81%). Derivatives 6a – g displayed greater activity than benznidazole. 6b ( R = Ph-O-(4-F-Ph)) and 6g ( R = Ph-O-(4-OCH 3 -Ph)) were the most active of all the synthesized compounds (IC 50 = 0.50 μM and IC 50 = 0.64 μM, respectively). Compounds 6h – n included a 3-fluoro substituent in the first phenyl ring, resulting in lower activity. The diaryl thioether compounds 6o – q exhibited lower anti- T. cruzi activity than diarylether analogs.

Source: ACS Omega

DOI: 10.1021/acsomega.5c08312