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

Abstract

A series of linear dipeptide derivatives (<b>4</b>-<b>10</b>) were prepared and evaluated as antimicrobial agents via the synthesis of <i>N</i>-(2-(2-hydrazinyl-2-oxoethylamino)-2-oxoethyl) nicotinamide (<b>4</b>). Compound <b>4</b> was reacted with 4-chlorobenzaldehyde or 4-hydroxybenzaldehyde, to give the hydrazones <b>5</b> and <b>6</b>, respectively. On the other hand, Compound <b>4</b> was coupled with phenylisocyanate or methylisothiocyanate to give Compounds <b>7</b> and <b>8</b>, respectively. The latter compounds (<b>7</b> and <b>8</b>) were coupled with chloroacetic acid to give oxazolidine (<b>9</b>) and thiazolidine (<b>10</b>), respectively. The newly synthesized dipeptide compounds were confirmed by means of their spectral data. The antimicrobial activity of the newly synthesized compounds <b>4</b>-<b>10</b> was evaluated by agar well diffusion, and they showed good activity. Compounds <b>4</b>, <b>5</b>, and <b>9</b> 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 <i>E. coli</i> and cytochrome P450 14 α-sterol demethylase (Cyp51) from <i>Candida albicans</i> active sites. The MolDock scores of the seven tested compounds ranged between -117 and -171 and between -107 and -179, respectively.