Design, Synthesis, Biological Evaluation and Molecular Docking Studies of New Thiazolidinone Derivatives as NNRTIs and SARS-CoV-2 Main Protease Inhibitors.

HIV-1 remains a major health problem worldwide since the virus has developed drug-resistant strains, so, the need for novel agents is urgent. The protein reverse transcriptase plays fundamental role in the viruses' replication cycle. FDA approved Delavirdine bearing a sulfonamide moiety, while thiazolidinone has demonstrated significant anti-HIV activity as a core heterocycle or derivative of substituted heterocycles. In this study, thirty new thiazolidinone derivatives (series A, B and C) bearing sulfonamide group were designed, synthesized and evaluated for their HIV-1 RT inhibition activity predicted by computer program PASS taking into account the best features of available NNRTIs as well as against SARS-COV-2 main protease. Seven compounds showed good anti-HIV inhibitory activity, with two of them, C1 and C2 being better (IC₅₀ 0.18 μΜ & 0.12 μΜ respectively) than the reference drug nevirapine (IC₅₀ 0.31 μΜ). The evaluation of molecules to inhibit the main protease revealed that 6 of the synthesized compounds exhibited excellent to moderate activity with two of them (B4 and B10) having better IC₅₀ values (0.15 & 0.19 μΜ respectively) than the reference inhibitor GC376 (IC₅₀ 0.439 μΜ). The docking studies is coincides with experimental results, showing good binding mode to both enzymes.