Design Synthesis and Biological Evaluation of Triazine Derivatives as Anti HIV Agents

Abstract

AIDS is a life threatening condition caused by Human Immunodeficiency Virus (HIV). AIDS is responsible for supressing immunity which spreads and transmits through blood and sex. According to WHO, around 41,758,381 people have already suffered from AIDS since 1986 with African and Asian countries have maximum number of HIV patients. A total number of 566,113 people had died due to AIDS and related illness at the end 0f 2019. HIV is a retrovirus which consist 3 integral enzymes responsible for its survival including reverse transcriptase, protease and integrase. Many drugs have approved in last 3 decades inhibiting these enzymes but most of drugs have problems of Drug resistance, side effects, toxicities and poor bioavailability. In course of our research to design and discover potent and bioactive anti-HIV agents, we have used ligand and structure based drug design approaches. A total number of 4 pharmacophore hypotheses were generated (3 Ligand based and 1 structure based). The common features obtained in pharmacophore were hydrogen bond donor, hydrogen bond acceptor and hydrophobic region. All these 4 models were validated and were used to search substructure from different databases. 3D-QSAR (CoMFA and CoMSIA) model was generated using 3 different alignment techniques including multifit alignment, docking based and distill based alignment for 63 compounds. A distill based alignment method was considered as better method according to different validation parameters and contour maps generated from CoMFA and CoMSIA models. A triazine ring was designed by incorporating pharmacophoric features and contour maps. The designed molecules were docked on HIV-I protease enzyme to predict binding affinities. In silico Pharmacokinetic and toxicities were also predicted using QikProp and OSIRIS. A total number of 32 compounds were synthesized and were characterized using FTIR, mass, 1H NMR and 13C NMR. The purity of all synthesized compounds were checked using HPLC. All synthesised compounds were evaluated fo