Synthesis and Biological Evaluation of Novel Aminochalcones as Potential Anticancer and Antimicrobial Agents

Abstract

A series of 18 aminochalcone derivatives were obtained in yields of 21.5-88.6% by applying the classical Claisen-Schmidt reaction. Compounds <b>4</b>-<b>9</b>, <b>14</b> and <b>16</b>-<b>18</b> with 4-ethyl, 4-carboxy-, 4-benzyloxy- and 4-benzyloxy-3-methoxy groups were novel, not previously described in the scientific literature. To determine the biological properties of the synthesized compounds, anticancer and antimicrobial activity assays were performed. Antiproliferative potential was evaluated on four different human colon cancer cell lines-HT-29, LS180, LoVo and LoVo/DX -using the SRB assay and compared with green monkey kidney fibroblasts COS7. Anticancer activity was described as the IC₅₀ value. The best results were observed for 2'-aminochalcone (<b>1</b>), 3'-aminochalcone (<b>2</b>) and 4'-aminochalcone (<b>3</b>) (IC₅₀ = 1.43-1.98 µg·mL^-1) against the HT-29 cell line and for amino-nitrochalcones <b>10</b>-<b>12</b> (IC₅₀ = 2.77-3.42 µg·mL^-1) against the LoVo and LoVo/DX cell lines. Moreover, the antimicrobial activity of all derivatives was evaluated on two strains of bacteria: <i>Escherichia coli</i> ATCC10536 and <i>Staphylococcus aureus</i> DSM799, the yeast strain <i>Candida albicans</i> DSM1386 and three strains of fungi: <i>Alternaria alternata</i> CBS1526, <i>Fusarium linii</i> KB-F1 and <i>Aspergillus niger</i> DSM1957. In the case of <i>E.</i> <i>coli</i> ATCC10536 almost all derivatives hindered the bacterial growth (∆OD = 0). Furthermore, the best results were observed in the presence of 4'-aminochalcone (<b>3</b>), that completely limited the growth of all tested strains at the concentration range of 0.25-0.5 mg·mL^-1. The strongest bacteriostatic activity was exhibited by novel 3'-amino-4-benzyloxychalcone (<b>14</b>), that prevented the growth of <i>E. coli</i> ATCC10536 with MIC = 0.0625 mg·mL^-1.