Synthesis, pharmacological screening and computational analysis of some 2-[l-Indol-3-yl]-A [[un]substituted phenylmethylidene] acetohydrazides and 2-[l-Indol-3-yl]-7V[[un]substituted benzoyl/2-thienylcarbonyl] acetohydrazides

ABSTRACT

The undertaken research was initiated by transforming 2-[l-Indol-3-yl]acetic acid [1] in catalytic amount of sulfuric acid and ethanol to ethyl 2-[l-Indol-3-yl]acetate [2], which was then reacted with hydrazine monohydrate in methanol to form 2-[l-Indol-3-yl]acetohydrazide [3]. Further, The reaction scheme was designed into two pathways where, first pathway involved The reaction of 3 with substituted aromatic aldehydes [4a-o] in methanol with few drops of glacial acetic acid to generate 2-[l-Indol-3-yl]-AD-[[un]substitutedphenylmethylidene]acetohydrazides [5a-o] and in second pathway 3 was reacted with acyl halides [6a-e] in basic aqueous medium [pH 9-10] to afford 2-[l-Indol-3-yl]-AD-[[un]substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides [7a-e]. All The synthesized derivatives were characterized by IR, EI-MS and !H-NMR spectral techniques and evaluated for their anti-bacterial potentials against Gram positive and Gram negative bacterial strains and it was found that compounds 7a-d exhibited antibacterial activities very close to standard Ciprofloxacin. The synthesized derivatives demonstrated moderate to weak anti-enzymatic potential against oc-Glucosidase and Butyrylcholinesterase [BChE] where, compounds 7c and 5c exhibited comparatively better inhibition against these enzymes respectively. Compounds 7a, 7d and 7e showed excellent anti-enzymatic potentials against Lipoxygenase [LOX] and their IC[5]o values were much lower than the reference standard Baicalein. Enzyme inhibitory activities were also supported by computational docking results. Compounds 5c, 7a, 7b and 7c also showed low values of % hemolytic activity as well, showing that these molecules were not toxic, indicating that these molecules can be utilized as potential therapeutic agents against inflammatory ailments