Synthesis, in vitro and in silico evaluation of new flavonoids-trifluoroacetylated amino acid conjugates as anti-acetylcholinesterase and anti-proliferative agents

A series of halogenated 3-hydroxyflavones (3HFs) (3a-3f) and their conjugates with two trifluoroacetylated amino acids, namely glycine and L-alanine, were synthesized and characterized by 1H NMR, 13C NMR and ESIHRMS. All the compounds were evaluated for their ability to inhibit the acetylcholinesterase enzyme and for their anti-proliferative effect against MCF-7, HCT-116 and OVCAR-3 cancer cell lines by standard MTT assay. Most of 3HFs-amino acids conjugates demonstrated promising cytotoxic activities, significantly higher than the corresponding 3HFs. Among them, compounds 8f and 9a showed the best cytotoxic activity against MCF-7 (IC50 = 5.5 and 5.3 & mu;M, respectively), HCT-116 (IC50 = 6.2 and 5.5 & mu;M, respectively) and OVCAR-3 (IC50 = 9.2 and 8.9 & mu;M, respectively). The derivatives 9c and 9b exhibited the highest anti-acetylcholinesterase activity with IC50 values of 50.1 and 55.2 & mu;M, respectively. The structure-activity relationship (SAR) is discussed based on molecular docking simulations.

Automated summary

A series of halogenated 3-hydroxyflavones and their conjugates with trifluoroacetylated amino acids were synthesized and characterized. Their ability to inhibit the acetylcholinesterase enzyme and their anti-proliferative effect against three cancer cell lines were evaluated. Most of the conjugates showed promising cytotoxic activities, and compounds 8f and 9a exhibited the best cytotoxic activity. The derivatives 9c and 9b exhibited the highest anti-acetylcholinesterase activity.