ArticleFuture medicinal chemistry2025
Enhancing thiazolide efficacy: C-4 aryl modifications drive selective SARS-CoV-2 inhibition.
Article in Future medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCOVID-19 highlighted urgent need for broad-spectrum antivirals. Nitazoxanide (NTZ), a broad-spectrum antiviral with an established safety profile, shows promise against SARS-CoV-2; however, its moderate potency and pharmacokinetic limitations necessitate the development of improved analogues.
methodsWe synthesized 24 thiazolide analogues, including novel molecules bearing 4´- or 5´-aryl substitutions, dual 4´,5´-modifications, or fused benzothiazole cores, and evaluated their
resultsAmong the analogues, 4´-aryl thiazolides (6d-6 g) and one dual-substituted thiazolide (7b) exhibited outstanding selectivity index (SI > 30), significantly surpassing NTZ (SI ≈ 14). The analogue 6e (3-OCF
conclusionsLipophilic, electron-withdrawing substituents at C-4 of the thiazole core markedly enhance antiviral potency and therapeutic potential. In particular, 4´-(PhOCF
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