Anti-HIV Drug Discovery, Development and Synthesis of Delavirdine: Review Article

Abstract

Viruses are the smallest infectious agents of animal and plant tissues. Viruses are totally dependent on living cells to survive as they utilize the host cell's own replication processes, in order to reproduce themselves. HIV is the causative agent of AIDS. HIV is an unusually difficult to treat because it incorporate its own genetic material into the genome of an infected host cell. It infects T cells that carry the CD4 antigen on their surface. Binding and fusion, reverse transcription, integration, transcription, assembly and budding are the major steps of the HIV life cycle. The HIV/AIDS disease is treated by interrupting the HIV life cycle with specially designed drugs. The discovery of effective drugs against HIV has focused on targeting various critical components of the replication cycle of HIV. Depending on the target within the HIV replicative cycle they interact with, anti-HIV compounds are categorized into six groups. These are: nucleoside (nucleotide) reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), cell entry inhibitors or fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The development of effective anti-HIV drugs is difficult due to wide variations in nucleotide and amino acid sequences. The development of anti-HIV drug passes through several important steps. This includes development from α-APA to ITU, ITU to DATA, DAPY to etravirine. Fosdevirine, lersivirine and rilpivirine are among the drugs that were undergoing clinical development and finally only rilpivirine was approved by FDA. The synthesis of delavirdine employs the use of heterocyclic rings like substituted pyridine and indole.