Pentamidine has been known to be active against a range of parasitic diseases including the malarial parasite which causes millions of deaths per year. There are two separate schools with regard to the primary target involved with the activity of this compound in P. falciparum - DNA minor groove, ferritoporphyrin IX (FPIX). This study aims at working with available pentamidine analogs in our database that are active against malaria to develop a probabilistic model that will be able to computationally evaluate target complementarity. Our protocol to develop such a model is to use GASP for conformational analysis and develop pharmacophore hypothesis followed by 3D QSAR to assist in target validation. Usage of pentamidine against diseases is prone to problems with respect to toxicity and oral availability. Target validation would open new pathways in terms of developing effective leads against Malaria and/or guide the synthesis of other scaffolds.
Dr. Prashanth Athri, Tidwell, R. R., and W Wilson, D., “Computational target validation based on 3-D QSAR for antiparasitic leads”, in American Chemical Society National Meeting, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA, 2006.