Synthesis and Biological Activities of Some New Benzotriazinone Derivatives Based on Molecular Docking; Promising HepG2 Liver Carcinoma Inhibitors.

In one-pot strategy, diazotization of methyl anthranilate followed by addition of amino acid ester hydrochloride, we have prepared methyl-2-(4-oxobenzotriazin-3(4)-yl)alkanoates -. Starting with hydrazides ,, -alkyl-2-(4-oxobenzotriazin-3(4)-yl)alkanamides -(-) and methyl-2-(2-(4-oxobenzotriazin-3(4)-yl)alkanamido)alkanoates -(-) were prepared via azide coupling. Hydrazones - were prepared via condensation of hydrazides , with 4-methoxybenzaldehyde, 4-dimethylaminobenzaldehyde, and/or arabinose. Molecular docking was done for synthesized compounds using MOE 2008-10 software. The compounds , , , , , and have the most pronounced strong binding affinities toward the target Fab-H receptor, whereas compounds , , , and have the most pronounced strong binding affinities toward the target vitamin D receptor. The in vitro antibacterial activities of the highest binding affinity docked compounds were tested against , , and . Majority of the tested compounds showed effective positive results against , while they were almost inactive against and The in vitro cytotoxic activities of the highest binding affinity-docked compounds were tested against the human liver carcinoma cell line (HepG2). Some compounds showed potent cytotoxic activity with low IC values, especially for (6.525 μM) and (10.97 μM than that for standard drug doxorubicin (2.06 μM).