Synthesis Molecular Docking Studies In Vitro Antimicrobial and Antifungal Activities of Novel Dipeptide Derivatives Based on N-(2-(2-Hydrazinyl-2-oxoethylamino)-2-oxoethyl)-Nicotinamide

摘要

A series of linear dipeptide derivatives (>4–>10) were prepared and evaluated as antimicrobial agents via the synthesis of N-(2-(2-hydrazinyl-2-oxoethylamino)-2-oxoethyl) nicotinamide (>4). Compound >4 was reacted with 4-chlorobenzaldehyde or 4-hydroxybenzaldehyde, to give the hydrazones >5 and >6, respectively. On the other hand, Compound >4 was coupled with phenylisocyanate or methylisothiocyanate to give Compounds >7 and >8, respectively. The latter compounds (>7 and >8) were coupled with chloroacetic acid to give oxazolidine (>9) and thiazolidine (>10), respectively. The newly synthesized dipeptide compounds were confirmed by means of their spectral data. The antimicrobial activity of the newly synthesized compounds >4–>10 was evaluated by agar well diffusion, and they showed good activity. Compounds >4, >5, and >9 gave the most promising activity in this study. Most of the tested compounds possessed MIC values ranging from 50 to 500 µg/mL. Furthermore, docking studies were carried out on enoyl reductase from E. coli and cytochrome P450 14 α-sterol demethylase (Cyp51) from Candida albicans active sites. The MolDock scores of the seven tested compounds ranged between −117 and −171 and between −107 and −179, respectively.