Macrophomina phaseolina mediated intramolecular trans-esterification of picrotoxinin and study of convulsant activity of transformed product

Abstract

Abstract Picrotoxinin (1), a stable natural neurotoxin containing a highly oxygenated polycyclic rigid compound, was first isolated from berries of Anamirta cocculus (L.) Wight & Arn. (formerly known as Menispermum cocculus). The present work was aimed to study the modification of the complex polycyclic structure of picrotoxinin (1) by using microbial transformation. Initially various fungi, such as Macrophomina phaseolina, Cunninghamella blakesleeana, Aspergillus flavus, Aspergillus niger, Cephalosporium aphidicola, and Fusarium lini were screened for their ability to modify the structure of 1. Only one fungus Macrophomina phaseolina was able to catalyze the structural modification of picrotoxinin (1). The subsequent whole cell catalysis produced an intramolecular trans-esterified product 2. The structure of the transformed product was deduced by spectroscopic, and single-crystal X-ray diffraction analyses. A comparative study on convulsant activity of picrotoxinin (1) and its metabolite 2 was conducted in mice. Interestingly, metabolite 2 showed a delayed convulsant activity, as compared to the compound 1.