Third-generation analogues of Guttiferone A

Résumé fourni par la source

This study introduces third-generation derivatives of guttiferone A, designed to enhance both bioactivity and selectivity against Plasmodium falciparum and Trypanosoma brucei . Following an optimized synthetic route, two dioxolane derivatives of 3,16-oxyguttiferone A were prepared: 14-monodioxolane-3,16-oxyguttiferone A ( 3 ) and 13,14-bisdioxolane-3,16-oxyguttiferone A ( 4 ). Biological evaluation revealed compound 3 to be the most effective, with a selectivity index (SI) of 457.1 against Trypanosoma brucei brucei strain and 57.1 against P. falciparum , significantly outperforming its precursors. Compound 4 also demonstrated substantial activity with an SI of 143.8 against T. brucei . These results highlight the potential of targeted structural modifications, particularly monodioxolane substitution, to improve the pharmacological profile of guttiferone A derivatives. • Synthesized third-generation guttiferone A derivatives with enhanced antiparasitic efficacy. • Compound 3 exhibited improved selectivity indices (SI) against T. brucei and P. falciparum . • Combined intramolecular cyclization and alkylation enhanced bioactivity and increased selectivity.

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