Studies on In Silico Synthesis of potentially active Anti HIV and Anti Psychotic drugs

Abstract

Objective: To carry out in silico synthesis of potentially active Anti-HIV drug which can mitigate the disease in its different stages and also CADD of anti Psychotic drugs. newlineHypothesis: With the application of computed techniques, drug like molecules with higher docking score than the standard available drug may be identified by increasing the hydrophobicity and the various mode of interactions with the amino acids of the disease-causing proteins present in the virus/bacteria/enzyme. newlineExperiment: The Computer Aided Drug Design (CADD) was carried out using different platform of the life science software Schrodinger suite of; the proteins of the HIV virus such as reverse transcriptase, protease and integrase were downloaded from www. rcsb.org. The co-crystallized molecules were removed and molecular docking studies of a large no. of molecule was done. The molecules were downloaded from ZINC.docking.org and screened by standard method; and in some molecule the change in structure was carried out by combinatorial approach. In this way some novel potentially, active molecules were searched. The virtual toxicity of the molecules was studied on discovery studio software of Dassault Ltd. newlineFindings: Following molecules were found virtually active and non-toxic: newlineA) Anti HIV newlineStage of HIV: 1st stage: protein of the virus: reverse transcriptase. Standard drug: Rilpivirine newlineDrug Candidates searched: From ZINC data base: ZINC70032481, ZINC70032478, ZINC70032479, ZINC05298157, ZINC52690626. newlineSecond Stage: protein of the virus: Protease: Standard drug: Darunavir. newlineDrug Candidates searched: ZINC59485580 and its modified structures by increasing hydrophobicity in the original structure. newlineThird Stage: protein of the virus: Integrase. Standard Drug: Dolutegravir. newlineDrug Candidates searched: ZINC13235071, ZINC05773622, ZINC00902842, ZINC13235074 and ZINC09419358 newlineB) Anti psychopathic: Standard Drug: PyP-19(under third stage of trial, developing by MERCK). Enzyme used: PDEA-10A9 (polydiesterase-10A) Drug Candidates searched: ZINC06025953 newline