Synthesis, molecular docking and antiviral screening of novel N'-substitutedbenzylidene-2-(4-methyl-5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-1(4H)-yl)acetohydrazides

N'-Substitutedbenzylidene-2-(4-methyl-5,5-dioxido-3-phenylbenzo[e]pyrazolo[4,3-c][1,2]thiazin-1(4H)-yl)acetohydrazides (7a-u) were synthesized through a multistep reaction. The final compounds were screened for anti-HIV-1 and cytotoxic activities. Among these compounds, 7l and 7m exhibited the most significant anti-HIV-1 activity with EC50 values of 5.4 and 3.3 mu M, respectively, while 7j showed moderate anti-HIV activity with an EC50 value 17.1 mu M. Molecular docking into HIV-1 Reverse Transcriptase also showed the best fit for 7l and 7m followed by 7j. In addition, compounds 7b, 7f, 7h, 7k, 7o, and 7s exhibited no toxicity in all the three cell lines used i.e., primary human PBM, CEM, and Vero cells, while 7e, 7g, 7i, 7n, 7p, 7q, and 7t exhibited no cytotoxic activity in primary human PBM cells. Moreover, it was found through molecular docking that compounds 7l, 7m, and 7j bound efficiently in the NTP-binding pocket of HIV-1 Reverse Transcriptase. The structure-activity relationship established on these results would facilitate the further development of new HIV inhibitors based on this skeleton.