Document Type
Article
Publication Date
1-1-2022
Journal / Book Title
Plos Neglected Tropical Diseases
Abstract
Filariasis, caused by a family of parasitic nematodes, affects millions of individuals through-out the tropics and is a major cause of acute and chronic morbidity. Current drugs are largely used in mass drug administration programs aimed at controlling the spread of disease by killing microfilariae, larval forms of the parasite responsible for transmission from humans to humans through insect vectors with limited efficacy against adult parasites. Although these drugs are effective, in some cases there are toxic liabilities. In case of loiasis which is caused by the parasitic eyeworm Loa loa, mass drug administration is contraindicative due to severe side effects of microfilariae killing, which can be life threatening. Our screening program and medicinal chemistry efforts have led to the identification of a novel series of compounds with potent killing activity against adult filarial parasites and minimal activity against microfilariae. A structural comparison search of our compounds demonstrated a close structural similarity to a recently described histone demethylase inhibitor, GSKJ1/4 which also exhibits selective adult parasite killing. We demonstrated a modification of his-tone methylation in Brugia malayi parasites treated with our compounds which might indicate that the mode of drug action is at the level of histone methylation. Our results indicate that targeting B. malayi and other filarial parasite demethylases may offer a novel approach for the development of a new class of macrofilaricidal therapeutics.
DOI
10.1371/journal.pntd.0010216
Montclair State University Digital Commons Citation
Kreiss, Tamara; Eck, Tyler; Hart, Brittany; Tummalapalli, Sreedhar; Rotella, David; and Siekierka, John, "A novel series of putative Brugia malayi histone demethylase inhibitors as potential anti-filarial drugs" (2022). Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works. 610.
https://digitalcommons.montclair.edu/chem-biochem-facpubs/610
Rights
This is an open access article distributed under the terms of the Creative Commons Attribution License.
Published Citation
Kreiss T, Eck T, Hart B, Tummalapalli S, Rotella D, Siekierka J (2022) A novel series of putative Brugia malayi histone demethylase inhibitors as potential anti-filarial drugs. PLoS Negl Trop Dis 16(3): e0010216. https://doi.org/10.1371/ journal.pntd.0010216