Inhibition Studies of Brugia malayi Dihydrofolate Reductase

Brugia malayi is a parasitic worm, which is one of the three causes of lymphatic filariasis. Lymphatic filariasis is a parasitic disease in which the worms live and infect a patient's lymph system. Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the reaction where dihydrofolic acid (DHF) is converted to tertrahydrofolic acid (THF). THF is important for synthesis of DNA. Literature studies suggest that DHFR is good drug target. If we can find a good inhibitor of B. malayi DHFR we can kill the worms and possibly find a cure for lymphatic filariasis. Current studies also suggest that antifolate compounds are inhibitors of B. malayi DHFR. Some of these compounds will be tested as potential inhibitors. In this study we are testing Aminopterin and Raltitrexed. A computational study has suggested that some green tea compounds are inhibitors of B. malayi DHFR. Green tea extract will be tested for inhibition of B. malayi DHFR. We have tested epigallocatechin gallate, epicatechin, epicatechin gallate, vitexin, and vitexcarpin to see if they are active inhibitors. If we find one that is an inhibitor, it will be studied further to determine other compounds with similar structures. We are also working on the crystallization of Bm DHFR to look at the three‐dimensional structure and determine exactly what inhibitor is best for B. malayi DHFR. The goal is to find and inhibitor for B. malayi DHFR and find a cure for lymphatic filariasis.