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 4–9, 14 and 16–18 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 (1), 3′-aminochalcone (2) and 4′-aminochalcone (3) (IC50 = 1.43–1.98 µg·mL−1) against the HT-29 cell line and for amino-nitrochalcones 10–12 (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: Escherichia coli ATCC10536 and Staphylococcus aureus DSM799, the yeast strain Candida albicans DSM1386 and three strains of fungi: Alternaria alternata CBS1526, Fusarium linii KB-F1 and Aspergillus niger DSM1957. In the case of E. coli ATCC10536 almost all derivatives hindered the bacterial growth (∆OD = 0). Furthermore, the best results were observed in the presence of 4′-aminochalcone (3), 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 (14), that prevented the growth of E. coli ATCC10536 with MIC = 0.0625 mg·mL−1.

Antimicrobial O-Alkyl Derivatives of Naringenin and Their Oximes Against Multidrug-Resistant Bacteria

“…They were tested against reference strains of E. coli, S. aureus, and B. subtilis from the American Type Culture Collection (ATCC). For example, 7,4′-di- O -isopropylnaringenin ( 5a ) was inactive against Escherichia coli , Bacillus subtilis, and S. aureus , whereas 7,4′-di- O -isopropylnaringenin oxime ( 5b ) exhibited activity against B. subtilis and S. aureus with MIC values equal to 6.25 μg/mL and 12.5 μg/mL, respectively [ 40 ]. The obtained results prompted us to carry out research on pathogens that are currently clinically relevant.…”

A Comprehensive Review of Aminochalcones

“…The inhibition activity of 1 against Escherichia coli ATCC 25923 and Candida albicans ATCC 10231 was as strong as the antibiotic sulfamerazine and as strong as sulfadiazine against Staphylococcus aureus ATCC 25922. The antibacterial and antifungal activities against different strains were also tested by Kozłowska et al [ 42 ], as shown in Table 2 .…”

“…Compound 1 causes complete growth inhibition in the case of S. aureus DSM799 and A. niger DSM1957 microbial strains and showed significant prevention of growth for the other strains [ 42 ]. The results of these investigations [ 40 , 42 ] show 1 as a promising antibacterial agent.…”

“…The activity for 8 was better than all derivatives, including chloro and methyl, tested for the Molt 4/C8, P388, and L1210 cells. The cell lines tested by Kozlowska et al [ 42 ] showed 8 to be decently potent. Among these cell lines, compound 8 exhibited the highest cytotoxic activity against the HT-29 cell line.…”

“…Kozlowska et al [ 42 ] tested the antimicrobial activity of 8 against two strains of bacteria, E. coli ATCC10536 and S. aureus DSM799; one strain of yeast, C. albicans DSM1386; and three strains of fungi, A. alternata CBS1526, F. linii KB-F1, and A. niger DSM1957. Compound 8 prevented the growth of E. coli with minimum inhibitory concentration (MIC) value equal to 0.25 mg/mL, two times stronger than reference oxytetracycline (MIC = 0.5 mg/mL).…”