Síntese de análogos da papulacandina D por simplificação molecular e avaliação de sua atividade antifúngica

Abstract

The papulacandins are a family of glycolipids isolated, by fermentation, from Papularia spherosperma, and that have shown potent in vitro antifungal activity against different strains of Candida sp. These compounds inhibit the enzyme â(1,3)-Dglucan synthase preventing the â(1,3)-D-glucan synthesis, a vital constituent of fungal cell wall. The papulacandins A, B e C are spiroglycosides derived from lactose andattached to two unsatured fatty acids by ester-bonds at C-3 and C-6 positions. The papulacandin D, the simplest member of the family, is a spiroglycoside derived from D-glucose and attached to an unsatured fatty acid at C-3 position. The less complex structure of papulacandin D as compared to the others compounds of the class and its lower antifungal activity was the inspiration for the design and synthesis of analogs of this compound, by molecular simplification, aimed at obtaining analogs with interesting antifungal activity, and establishing more knowledge about the chemical structure-biological activity relationship of these compounds.Nine new analogs of the papulacandin D were synthesized. These compounds and some synthetic intermediaries were evaluated against Candida albicans, Candida krusei, Candida parapsilosis and Candida tropicalis. Two papulacandin D analogs showed 50% inhibition growth of Candida tropicalis to 200 ìg/mL. Two intermediaries showed 50% inhibition of Candida albicans and Candida tropicalis growth, also to 200 ìg/mL.