Synthesis and evaluation of some new imidazolone bearing phthalyl and tosyl amino acids moities as anti-cancer agents supported by molecular docking

Abstract

A facile and convenient synthesis of imidazolone-incorporated phthalyl and/or p-tosyl amino acid derivatives was described. The reaction of oxazolone derivative 2 with p-phenylenediamine followed by coupling of the free amino group in imidazolone 3 with various protected amino acids such as threonine, valine, alanine, serine, glutamine, glycine, leucine, phenylalanine, arginine, methionine, and aspartic acid using N,N-dicyclohexylcarbodiimide (DCC) as the dehydrating agent afforded the desired compounds 4a-j and 6a-j. Deprotection of the amino group in N-phthaloyl derivatives 4a-j was accomplished with good yields through refluxing with an ethanolic solution of hydrazine hydrate to afford unprotected aminoacyl derivatives 5a-j. All chemical structures of imidazolone derivatives were elucidated by elemental analysis as well as spectral data (IR, MS, and 1H NMR spectra). The anti-cancer activity of some synthesized compounds was evaluated against carcinogenic human cell lines, namely, human prostate cancer (PC3) and mammary gland breast cancer (MCF-7), and some of them showed promising cytotoxicity comparable with the standard drug doxorubicin (DOX). A molecular docking study between various receptors and the target compounds was performed, and it confirmed a good correlation between their strength of receptor-binding and anti-cancer activities.