Perovskone, a potential antiprotozoal hit compound, quantification and derivatization

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Perovskone, an isoprenoid, exhibits notable antiprotozoal activities.
• Salvia hydrangea is identified as the primary natural source of perovskone.

Purpose of the Study:

• Quantify perovskone in Salvia hydrangea from different regions and years.
• Assess perovskone levels in related Salvia species.
• Synthesize perovskone derivatives to enhance antiparasitic capabilities.
• Evaluate the in vitro efficacy and cytotoxicity of perovskone and its derivatives.

Main Methods:

• Quantitative analysis of perovskone in various plant parts.
• Chemical synthesis of semi-synthetic perovskone derivatives.
• Structural elucidation using 1D/2D NMR and HRMS.
• In vitro assays against Leishmania donovani, Trypanosoma brucei, Plasmodium falciparum, and Trypanosoma cruzi.
• Cytotoxicity assessment using rat L6 skeletal myoblasts.

Main Results:

• Perovskone concentration was highest in S. hydrangea leaves and stems (0.053% dry weight).
• Perovskone was below the limit of quantification in roots and other Salvia species.
• Derivative 3 showed significant anti-Plasmodium falciparum activity (IC50 0.08 µM, SI 80), outperforming perovskone.
• No significant variation in perovskone levels was observed across different collection years.

Conclusions:

• Salvia hydrangea is a viable source for perovskone extraction.
• Perovskone derivatives hold promise for developing novel antiprotozoal lead compounds.
• Derivative 3 represents a potent anti-malarial candidate with high selectivity.