Perovskone, a potential antiprotozoal hit compound, quantification and derivatization.

Perovskone is a structurally fascinating and intricate isoprenoid with significant antiprotozoal activities. This study quantified perovskone in various parts of its primary source, Salvia hydrangea, collected from two distinct climatic regions over three years. Its quantity was also assessed in three other Salvia species that are taxonomically close to S. hydrangea. Moreover, semi-synthetic derivatives (3-5) were synthesized from perovskoneto improve its antiparasitic capabilities. 1D and 2D NMR and HRMS were used to identify the structures, and perovskone to then the compounds were evaluated in vitro against Leishmania donovani, Trypanosoma brucei, Plasmodium falciparum, and Trypanosoma cruzi and cytotoxicity was assessed in rat L6 skeletal myoblasts. Perovskone was the highest in S. hydrangea leaves and stems at 0.053% dry weight (1.5% dry extract), followed by flowers at 0.04% of dry weight. It was below the limit of quantification (LOQ) in roots and in other Salvia species. No significant difference was observed between samples of different years. Derivative 3 demonstrated significant efficacy against P. falciparum (IC50 0.08 µM, selectivity index 80), indicating a two-fold increase in activity compared to perovskone and matching the effectiveness of artemisinin and chloroquine. Given the results, S. hydrangea is a viable source for extracting perovskone and developing a new class of antiprotozoal lead compounds.