Catechin Derivatives as Inhibitors of Programmed Cell Death 1 Receptor (Pd –1), a Predominant Factor of Homo Sapiens in the Development of Oral Squamous Cell Cancer

Abstract

One of several mechanisms of tumour-mediated immune suppression is the expression of co-inhibitory molecules by tumour. Upon engagement to their ligands these molecules can suppress effector lymphocytes in the periphery and in the tumour microenvironment. The PD-1 is one of the central signalling molecules that may inhibit T cell immunity when bound to its ligands (PD-L1 or PD-L2) by inducing T cell apoptosis and anergy. PD- L1 expression reduces the number of T cells in human oral squamous cell carcinoma. Further it has been suggested that the development of a strategy to block the interactions of PD-L1 with PD-1 would be a useful tool for inhibiting tumour growth. The three-dimensional structure of GTF-SI was retrieved from RCSB database. The possible binding sites of PD-1 were searched using binding site prediction 3DLIGANDSITE, an online tool. A total of 500 ligands in 2D format were generated from the basic structure of catechin with the help of software ACD chemsketch. Rapid virtual screenings of these compounds were performed in the docking tool iGEMDOCK v2.0. The molecular docking of ligands was performed using AutoDock 4.0 software. In the present study, (2S, 3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol has found to have very good inhibitory property based on molecular docking study. Further the compound shows a good ADMET properties based on studies in OSIRIS. Hence it is concluded that (2S,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H- chromene-3,5,7-triol is an excellent drug candidate in the control of oral squamous cell carcinoma.