Synthesis, in vitro and in silico studies of novel N-benzoyl EF24 analogs as potential anticancer agents.

Introduction: EF24, a synthetic curcumin derivative, is effective against different forms of cancers but its derivatives are underdeveloped, particularly to improve cytotoxicity and drug-receptor interactions in colorectal cancer.

Areas covered: Nine N-benzoyl EF24 analogs were prepared and identified by Fourier transform infrared (FT IR), proton nuclear magnetic resonance (¹H NMR), and mass spectra. Cytotoxicity against the HT-29 cancer cell was screened by 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide (MTT) assay at 24 and 48 hours. Molecular docking on glyoxalase I compared binding interactions. Compounds 4, 5, 7, and 10 were significantly cytotoxic with compound 10 being more cytotoxic than EF24 and cisplatin. Compound 10 was found to have maximum binding affinity by docking with active-site residues.

Expert opinion/commentary: The N-benzoyl EF24 analogs, especially compound 10, have shown encouraging cytotoxicity and favorable drug-receptor interaction, suggesting their clinical utility as agents against colorectal cancer. Pharmacokinetic and in vivo explorations are also needed to further advance the compounds for clinical application.