In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410

Abstract

In the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of Penicillium sp. FKI-4410. Two were known compounds, puberulic acid and stipitatic acid. Three were new analogs of puberulic acid, designated viticolins A–C. Among them, puberulic acid exhibited potent antimalarial inhibition, with IC₅₀ values of 0.01 μg ml⁻¹ against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro. Furthermore, puberulic acid showed weak cytotoxicity against human MRC-5 cells, with an IC₅₀ value of 57.2 μg ml⁻¹. The compound also demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalarial compound.