Synthesis, characterization, molecular docking and molecular dynamics simulations of benzamide derivatives as potential anti-ovarian cancer agents

Abstract

A novel (E)-N-cinnamoyl-4-methoxybenzamide (CMB) and (E)-3‑chloro-N-cinnamoyl-4-methoxybenzamide (CCMB) were synthesized and characterized by using Fourier-transform infrared spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) and Ultraviolet–visible spectroscopy. Theoretical vibrational spectra, NMR and some electronic properties of CMB and CCMB have been calculated using Density Functional Theory (DFT), B3LYP functional with a 6–311G++ basis set. UV–Vis spectra obtained by Time-dependent-DFT/ polarizable continuum model (PCM) methods were also compared to experimentally reported spectra. In addition, the molecular electrostatic potential (MEP) and frontier molecular orbitals (FMOs) were calculated and discussed for the title compounds. The present study examined the use of two molecules as matrix metalloproteinases (MMPs) inhibitors for the treatment of ovarian cancer. Molecular docking results show that both CCMB and CMB bind to MMP-2 with higher affinity (-8.50 and -8.35 kcal/mol) than MMP-1 (-8.24 and -8.07 kcal/mol). According to MD simulations, values of the solvent accessible surface area changed very little from the title molecules. During the MD simulation, the number of H-bonds formed between CMB and CCMB towards targets was also determined.