Project Shuddhikaran (P.S.)

This research proposal focuses on the design, synthesis, and biological evaluation of novel compounds as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV infection. Despite the success of highly active antiretroviral therapy (HAART), the growing resistance to first-generation NNRTIs—such as nevirapine and efavirenz—due to common mutations like K103N and Y181C presents a serious clinical challenge. To address this, the study aims to develop structurally innovative NNRTIs incorporating promising heterocyclic scaffolds such as pyrimidine, indole, triazole, and benzothiazole. The compounds will be rationally designed using molecular docking, followed by synthesis through standard organic protocols and full characterization using FTIR, NMR, Mass Spectrometry, and Elemental Analysis. Further, their anti-HIV activity will be assessed in vitro using MT-4 cell lines infected with wild-type and mutant HIV-1 strains, along with computational evaluation (ADMET) to identify potent lead molecules. The study also includes structure-activity relationship (SAR) analysis and mechanism-of-action studies. This integrated approach aims to discover next-generation NNRTIs with enhanced resistance profiles, paving the way for effective HIV therapy.