~ 1858 ~ International Journal of Chemical Studies 2018; 6(6): 1858-1868 P-ISSN: 2349–8528 E-ISSN: 2321–4902 IJCS 2018; 6(6): 1858-1868 © 2018 IJCS Received: 25-09-2018 Accepted: 30-10-2018 Om Prakash Veterinary Polytechnic, Surajpur, Chhattisgarh Kamdhenu Vishwavidyalaya, Durg, Chhattisgarh, India Shankarlingam Gomathinayagam Department of Veterinary Parasitology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Science University, Chennai, Tamil Nadu, India Tirunelveli Jeyagopal Harikrishnan Tamil Nadu Veterinary and Animal Science University, Chennai, Tamil Nadu, India Muthusamy Raman Transboundary Research Platform for Veterinary Biological, Tamil Nadu Veterinary and Animal Science University, Chennai, Tamil Nadu, India Velayudham Pandiyan Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India Samapika Sahoo Department of Veterinary Parasitology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Science University, Chennai, Tamil Nadu, India Correspondence Om Prakash Veterinary Polytechnic, Surajpur, Chhattisgarh Kamdhenu Vishwavidyalaya, Durg, Chhattisgarh, India Identification of analogue compounds of P- glycoprotein associated anthelmintics resistance reversal agents through cheminformatics approaches Om Prakash, Shankarlingam Gomathinayagam, Tirunelveli Jeyagopal Harikrishnan, Muthusamy Raman, Velayudham Pandiyan and Samapika Sahoo 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. Keywords: anthelmintic resistance, cheminformatics, haemonchus, p- glycoprotein, docking Introduction In the continued absence of commercial vaccines, the use of broad-spectrum anthelmintics has been the primary method to control the pathogens in cattle and sheep for over 50 years [1, 2] . The use of anthelmintics in intensive farming has followed swiftly by the emergence of anthelmintic resistance (AR) which is now an emerging phenomenon in parasitic nematodes of sheep, goats, horses, and cattle [3] . 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 [4] . Resistance to the majority of the anthelmintics including the Benzimidazole [5, 6] , Salicylanilides [6] , Macrocyclic lactones [5, 7] were reported. The key to control anthelmintic resistance in H. contortus is to understand various mechanisms that may be involved, for each class of anthelmintics has a known different target. There are three main groups of mechanisms: those that change the binding sites of drugs, those that detoxify, and those that involve the active efflux of drugs by membrane transporters [8, 9] . The mechanism that is primarily considered to be involved in resistance to macrocyclic lactones is the detoxification process of P- glycoproteins. P-glycoproteins (Pgps) are efflux transporters which actively transport compounds, including drugs, across membranes [10] . The primary function of Pgp is to protect the organism by actively pumping toxic substances out of its cells [11] . P-glycoproteins have been identified in H. contortus and the full cDNA sequence has been obtained [12] . The mechanism believed to be associated with anthelmintic resistance in H. contortus is the overexpression of Pgp. Both benzimidazole and ivermectin-resistant strains of H. contortus have been found to possess Pgp alleles in higher frequency than susceptible strains. Pgp may modulate benzimidazole concentration at the target site [9] . A relationship between Pgp and benzimidazole resistance was indirectly demonstrated through the use of the Pgp inhibitor Verapamil [13, 14] . Verapamil is a calcium channel blocker, which actively inhibits the Pgp drug-binding domain. In the presence of Verapamil, the toxicity of the drug increased and the benzimidazole resistance could be partially reversed [12] . A role for P-glycoprotein (P-gp)