Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity

Abstract

In our investigation, we concentrated on naringenin (<b>NG</b>)-a widely studied flavanone that occurs in citrus fruits. As a result of a reaction with a range of alkyl iodides, 7 novel <i>O</i>-alkyl derivatives of naringenin (<b>7a</b>⁻<b>11a</b>, <b>13a</b>, <b>17a</b>) were obtained. Another chemical modification led to 9 oximes of <i>O</i>-alkyl naringenin derivatives (<b>7b</b>⁻<b>13b</b>, <b>16b</b>⁻<b>17b</b>) that were never described before. The obtained compounds were evaluated for their potential antibacterial activity against <i>Escherichia coli</i>, <i>Staphylococcus aureus</i>, and <i>Bacillus subtilis</i>. The results were reported as the standard minimal inhibitory concentration (MIC) values and compared with naringenin and its known <i>O</i>-alkyl derivatives. Compounds <b>4a</b>, <b>10a</b>, <b>12a</b>, <b>14a</b>, <b>4b</b>, <b>10b</b>, <b>11b</b>, and <b>14b</b> were described with MIC of 25 µg/mL or lower. The strongest bacteriostatic activity was observed for 7-<i>O</i>-butylnaringenin (<b>12a</b>) against <i>S. aureus</i> (MIC = 6.25 µg/mL). Moreover, the antitumor effect of flavonoids was examined on human colon cancer cell line HT-29. Twenty-six compounds were characterized as possessing an antiproliferative activity stronger than that of naringenin. The replacement of the carbonyl group with an oxime moiety significantly increased the anticancer properties. The IC₅₀ values below 5 µg/mL were demonstrated for four oxime derivatives (<b>8b</b>, <b>11b</b>, <b>13b</b> and <b>16b</b>).