Effects of valproic acid on fatty acid production in microorganisms and bioactive compounds from feroniella lucida (scheff.) Swingle and termite-associated fungus ISFB10

Abstract

Valproic acid or valproate (VPA) is a drug for the treatment of epilepsy, bipolar disorder, migraine headaches and neuropathic pain. Unfortunately, VPA has many side effects. In this work, it was found that productions of some fatty acids were significantly affected by VPA at the concentration of 100 μM. Further exploration of VPA on fatty acid production in microorganisms including fungi, yeast, and bacteria, as well as representative gut microbiome. This work showed that VPA could enhance, reduce or completely inhibit the production of some fatty acids. VPA could induce the production of trans-9-elaidic acid that was previously found to have cellular effects in human macrophages. Moreover, VPA was found to inhibit the production of some polyketides produced by a model fungus. This work also investigated bioactive compounds from a plant, Feroniella lucida (Scheff.) Swingle and a termite-associated fungus ISFB10. Candicine (7) and candicine derivative (8) were isolated from spine part of F. lucida. Compound 8 exhibited weak cancer chemoprevention activity in the xanthine oxidase assay (XXO) with an IC50 value of 473.8±13.4 μM. Roridin A (9) and verrucarin A (10) were isolated from the termite-associated fungus ISFB10. Compounds 9 exhibited strong cytotoxic activities toward HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC50 values of 0.016±0.0007, 0.0055±0.0001, 0.005±0.0003 and 0.024±0.002 µM, respectively. Compounds 10 also exhibited strong cytotoxic activities toward HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC50 values of 0.014±0.0005, 0.0047±0.0005, 0.008±0.0002 and 0.019±0.001µM, respectively. Unfortunately, compounds 9 and 10 were also exhibited strong cytotoxic activity toward normal cell line MRC-5 with IC50 values of 0.038±0.006 and 0.012±0.0004, respectively.