Investigation of microbial extracts as a source of neurological agents

Graduation date: 2010This study tested natural products from cyanobacteria from the Red Sea in Egypt and marine tunicates from the Algoa Bay in South Africa. Products from marine organisms have been used as lead compounds for the synthesis of new drugs because of their biological activity mechanism. Specifically, these products may contain compounds that display voltage-gated sodium channel activity, a feature of some medications for nervous system conditions such as epilepsy (Neurontin, Tregetol, Keppra) or cardiac arrhythmias (Norpace, Xylocaine, Rythmol). Initially, products and fractionations were screened in mouse neuroblastoma cells (Neuro-2A) and cytotoxic activity was measured in an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay after a 24 hour period. The most active extracts identified in the cytotoxicity activity assay were selected as candidates for voltage-gated sodium channel activity measurements. This assay was a modified form of the initial MTT assay that exposed cells to known neurotoxins, ouabain and veratridine, to create a high concentration of sodium ions inside the cells. Extracts with voltage-gated sodium channel activity would either rescue the cells by inhibiting the channel, or activate the channel and kill the cells. The cytotoxicity assay identified 21 products, crude and fractionated, as somewhat cytotoxic