Bioactive Derivatives of Isopropylstilbene from Mutasynthesis and Chemical Synthesis

Isopropylstilbene is a natural product from Photorhabdus luminescens TT01, with multiple biological activities. A mutant deficient in the production of both anthraquinones and cinnamic acid was constructed, thus giving a clean background according to UV detection. This anthraquinone and stilbene deficient (ASD) mutant was used in mutasynthesis experiments to obtain new stilbene derivatives, which were detected by GC–MS. The structures of the new derivatives were confirmed by detailed MS analysis and then chemically synthesised; all of the natural and synthetic compounds were tested against protozoa that cause tropical diseases. Two compounds obtained by mutasynthesis showed the highest activity against Trypanosoma cruzi, the causative agent of Chagas disease, and Leishmania donovani, which causes leishmaniasis. It's just not natural! The production of new isopropylstilbene derivatives was achieved by mutasynthesis with a Photorhabdus ASD (anthraquinone and stilbene deficient) mutant, blocked in anthraquinone and cinnamic acid biosynthesis. Chemical synthesis of selected compounds allowed for their biological evaluation, which led to compounds with better activity than the natural products.