There is an urgent need for new naturally occurring and/or naturally derived chemical structures for drug development. The biotransformation of two bioactive guaiane-type sesquiterpene lactones, ludartin and estafietin, by filamentous fungi of the genera Aspergillus and Penicillium and by extremophile bacteria of the genera Rhodococcus, Acinetobacter, Streptomyces, and Citricoccus led to the isolation of three new and four known derivatives. The structures were determined based on data obtained from HRESIMS and 1D/2D NMR spectroscopy. The predominant reactions from both eukaryotic and prokaryotic biocatalysts were stereoselective epoxide opening and chemical and regio- and stereoselective double bond reduction, though the fungi were more efficient than the bacteria. Substrates and six selected metabolites were subjected to in vitro evaluation for antiproliferative effects against six human solid tumor cell lines. The derivative 3α,4β-dihydroxy-estafietin showed significant activity against HBL-100, HeLa, and SW1573 cell lines, justifying a more specific, in-depth evaluation of its scope as an anticancer candidate molecule.
Furque et al. (Tue,) studied this question.