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

ABSTRACT: 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-OCH₃-Ph)) were the most active of all the synthesized compounds (IC₅₀ = 0.50 μM and IC₅₀ = 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 acti

SUBMITTER: Santos LBB 

PROVIDER: S-EPMC12658631 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature