Biotransformation of Two Guaiane-type Sesquiterpene Lactones with Filamentous Fungi and Extremophile Bacteria

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 <i>Aspergillus</i> and <i>Penicillium</i> and by extremophile bacteria of the genera <i>Rhodococcus, Acinetobacter, Streptomyces</i>, and <i>Citricoccus</i> 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 <i>in vitro</i> evaluation for antiproliferative effects against six human solid tumor cell lines. The derivative 3<i>α</i>,4<i>β</i>-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.