Design, microwave-assisted synthesis, biological evaluation, molecular docking and ADME studies of pyrrole-based hydrazide-hydrazones as potential antioxidant agents

In this study, one novel N-pyrrolyl carboxylic acid (3), the corresponding hydrazide (5), and four new hydrazide-hydrazones (5a-d) bearing electron donating moieties were designed, synthesized, fully elucidated by 1H NMR, FT-IR, HRMS. The produced in five steps, which optimized applying microwave heating. microwave-assisted synthesis significantly decreased reaction times increased yields of title molecules. addition, all compounds assessed for their radical scavenging properties employing DPPH ABTS assays. most promising agent was obtained after condensation (5) with a 3,5-dimetoxy-4-hydroxybenzaldehyde (5d). latter compound showed better antioxidant than Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) could serve as prominent lead structure future optimization an agent. A possible binding conformation 5d active site NADPH oxidase also identified through molecular docking simulations. Analysis major interactions importance hydroxyl moiety activity. Finally, virtual calculations ADME synthesized displayed good drug-like properties. Overall, synthetic protocol MW irradiation employed. newly ethyl (E)-5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3,5-dimethoxybenzylidene)hydrazineyl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate (5d) found to possess radical-scavenging capacity, identifies it development antioxidants.