Phenyl hydrazone bearing pyrazole and pyrimidine scaffolds: design and discovery of a novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) against HIV-1 and their antibacterial properties

A novel series of phenyl hydrazone bearing pyrazole and pyrimidine hybrid compounds has been designed using the molinspiration toolkit based on Lipinski's rule of five and developed via sequential reactions starting from the diazotization of different anilines and further active methylation with acetyl acetone, ethyl acetoacetate and ethyl cyanoacetate to generate hydrazono derivatives. The target hybrid compounds were synthesized on cyclisation of the resulting hydrazono derivatives with hydrazine, phenyl hydrazine and urea. These molecules have been subsequently tested for anti-HIV activity using TZM-bl cell lines. The MTT assay was also carried out for the cytotoxicity determination of the active compounds. Further, to exemplify the key structural features of the molecules, a molecular docking analysis of the most active compounds was performed at the NNIBP of the HIV-RT protein. The antibacterial activity of the target compounds was also determined against a panel of four Gram-positive and four Gram-negative human pathogens. All molecules showed a potent anti-HIV activity along with a prominent inhibition of bacterial organisms.