Identification of analogue compounds of P-glycoprotein associated anthelmintics resistance reversal agents through cheminformatics approaches

Abstract

The use of anthelmintics in intensive farming has followed swiftly by the emergence of anthelmintics resistance (AR) which is now an emerging phenomenon in parasitic nematodes of sheep, goats, horses, and cattle. AR is defined as a genetically transmissible trait in which the sensitivity to a particular drug is lost in a population of worms over time. Cheminformatics studies were carried out to find out the P glycoprotein modulators/inhibitors from plant compounds/chemicals sources. Three dimensional structure of Pgp was designed using the sequences from NCBI. Five models of Pgp were received. Based on I-TASSER modeling and RAMPAGE score Pgp model 1 was selected and molecular docking was done to interact with 36 plant compounds/chemicals using Accelrys Discovery Studio client 2.5. Based on the best molecular docking score (more than 90 interactions), Curcumin, Quercetin, Kaempferol, Phloretin, Verapamil and Loperamide with molecular docking scores of 98.324, 96.073, 95.47, 94.895,93.453 and 92.807 were selected.