Malaria claims about a million deaths worldwide annually. The widespread resistance to current drug therapies is of major concern and necessitates the need for identification of new drug targets and new drugs. Malaria parasite needs to degrade the host cell hemoglobin to obtain amino acids for its growth during its development in erythrocytes. M1 alanyl-aminopeptidase (PfAPN) is an enzyme involved in the terminal stages of hemoglobin digestion to generate an amino acid pool within the parasite, and this enzyme has been validated as a potential drug target. To develop selective and effective inhibitors against PfAPN, we designed and synthesized a host of Piperidinyl Sulfamides basedcompounds. These molecules displayed inhibition of the recombinant PfAPN at low micromolar concentrations. To assess if these compounds also affect parasite growth, the most lethal human malaria parasite P. falciparum was grown in the presence of varying concentration of these compounds, and IC50 concentrations for each compound were determined. Similar to the enzyme inhibition, these molecules showed parasite growth inhibition with IC50 values in the low micromoles. Structural studies are in progress to understand their selectivity for PfPAN and improve their potency.

Design and synthesis of piperidinyl sulfamides against malarial aminopeptidase N, with micromolar efficacy against the parasite

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.