Synthesis, characterization & molecular docking studies of rationally designed azobenzene-Derived 5-oxoimidazoline...

The study aimed to design the series of azobenzene-induced 5-oxoimidazoline moiety, represents as a promising structural framework for the development of a new class of antimicrobial agents, supported by molecular docking studies.

Two series of compounds (10 in each series) were synthesized through a multistep procedure beginning with diazotization of 2-nitroaniline, followed by coupling with methyl paraben to yield azobenzene compound (9), which were subsequently refluxed with hydrazine hydrate to afford the hydrazide intermediate (11). Reaction of compound (11) with substituted acetophenones 12(A1-A5) and aldehydes 12(A6-A10) produced schiff bases 13(S1-S10), which upon refluxing with amino acids (glycine and alanine) furnished the desired final compounds 14(M1-M10)and 15(M1-M10). The compounds were screened for in-vitro antimicrobial activity & molecular docking studies were carried out to investigate ligand - protein interactions and to predict the most probable binding conformations.

Compounds 14M6 (MIC = 0.55 & 0.45 µg/ml, ΔG = -6.093), 14M9 (MIC = 0.38 µg/ml, ΔG = -5.928), 15M9 (MIC = 0.40 µg/ml, ΔG = -6.084) showed best anti-fungal activity displaying best docking score (PDB ID: 3LD6). The most active anti-bacterial compounds included 14M8 (MIC = 0.70 & 0.88 µg/ml, ΔG = -5.832), 14M9 (MIC = 0.54, 0.72& 0.39 µg/ml, ΔG = -5.755 & -5.845), 15M8 (MIC = 0.34, 0.75& 0.55 µg/ml, ΔG = -5.683 &-5.894), 15M9 (MIC = 0.65& 0.44 µg/ml, ΔG = -5.573) with best docking score (PDB ID: 2XCT & 6M1S).

Compounds 14M6, 14M8, 14M9, 15M8 & 15M9 emerged as the most promising antimicrobial candidates, establishing them as potential lead molecules for further optimization and drug development.