SCREENING OF PROTON PUMP INHIBITOR ANTAGONIST FOR HUMAN FOLATE TRANSPORTER

Abstract

Folate transport is crucial for proper proliferation of cells. Amongst humans, the folate is procured from external sources since it is not synthesized in the human body. Hence specific transporters are involved in uptake of folate. For the malignant cancerous cells, these folate are crucially required on very frequent rate to fulfil the rapid proliferation of the cancerous cells. In the present study, we have comparatively studied three antagonist drug molecules which could be a potential candidate to inhibit the folate uptake by the human Proton Coupled folate transporter (hPCFT). These candidate antagonist include Pemetrexed, 2-[(4-Aminobenzoyl)amino] pentanedioate-pABA-Glu and Methotrexate. Out of these three antagonist drug, the Pemetrexed molecule was observed to specifically bind to the key active site loop (G155XXG158) of the hPCFT transporter. The Binding energy of the Pemetrexed was also comparatively lowest (-7.6 kcal/mol). Hence from the present study we conclude that the Pemetrexed antagonist drug is more e fficient to inhibit folate transport as compared to the 2-[(4-Aminobenzoyl)amino]pentanedioate-pABA-Glu and Methotrexate antagonist drug molecules.