Synthesis, pharmacological screening & computational analysis of some 2-(1H-Indol-3-yl)-N'-[(un)substituted phenylmethylidene] acetohydrazides & 2-(1H-Indol-3-yl)-N'-[(un)substituted benzoyl/2-Thienylcarbonyl]acetohydrazides

• Published in: Pakistan Journal of Pharmaceutical Sciences
• Main Author: Rubab K.; Abbasi M.A.; Aziz-Ur-Rehman; Siddiqui S.Z.; Shah S.A.A.; Ashraf M.; Qurat-Ul-Ain; Ahmad I.; Lodhi M.A.; Ghufran M.; Shahid M.; Fatima H.
• Format: Article
• Language: English
• Published: Pakistan Journal of Pharmaceutical Sciences 2017
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021327600&partnerID=40&md5=e439ad5521543eaefcd306854a0c5522

The undertaken research was initiated by transforming 2-(1H-Indol-3-yl)acetic acid (1) in catalytic amount of sulfuric acid and ethanol to ethyl 2-(1H-Indol-3-yl)acetate (2), which was then reacted with hydrazine monohydrate in methanol to form 2-(1H-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-(1H-Indol-3-yl)-N-[(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-(1H-Indol-3-yl)- N-[(un)substitutedbenzoyl/2-Thienylcarbonyl]acetohydrazides (7a-e). All The synthesized derivatives were characterized by IR, EI-MS and 1H-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 antienzymatic potential against α-Glucosidase and Butyrylcholinesterase (BChE) where, compounds 7c and 5c exhibited comparatively better inhibition against these enzymes respectively. Compounds 7a, 7d and 7e showed excellent antienzymatic potentials against Lipoxygenase (LOX) and their IC 50 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.