Antiproliferative and antibacterial activity of some glutarimide derivatives

Abstract

<p>Antiproliferative and antibacterial activities of nine glutarimide derivatives (<b>1</b>–<b>9</b>) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound <b>7</b> (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC₅₀ = 9–27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds <b>1</b>, <b>2</b>, <b>4</b>, <b>6</b>–<b>8</b> and <b>9</b> inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound <b>9</b> (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against <i>Bacillus cereus</i> (MIC 0.625 mg/mL; 1.97 × 10⁻³mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.</p