Molecular Docking Study, Synthesis and Characterization of New Hybrid Anthracene-Thiophene Compounds with Chalcone and Pyridine Scaffolds

Abstract

Breast cancer is a major health problem with an increasing number of cases over the years. Few classes of anticancer agents have been developed, but they established toxic effects on normal cells. In this study, a new hybrid anthracene-thiophene chalcone 1 has been synthesized via a Claisen-Schmidt condensation of substituted anthracene aldehyde and a thiophene ketone. The cyclo-condensation reaction of chalcone 1 formed a new anthracene-thiophene pyridine 2. The synthesized compounds were structurally characterized by Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. The molecular docking activities using AutoDock 4.2 software were performed to study the intermolecular interactions between these compounds with breast cancer protein, 3ERT as the estrogen receptor-α. Chalcone 1 showed free binding energy of -9.81 kcal/mol, while pyridine 2 exhibited better free binding energy of -10.45 kcal/mol against 3ERT protein. The interactions in pyridine 2 include one hydrogen bonding with MET343 amino acid and several hydrophobic interactions such as π-σ interaction with LEU384, π-anion interaction with ASP351, π-alkyl interactions with ALA350, LEU346, LEU391, LEU525, and MET388 and also a π-sulfur interaction with MET343. Chalcone 1 has only noncovalent interactions such as π-σ interaction with THR347 and π-alkyl interactions with ALA350, LEU346, LEU349, LEU387, LEU391, LEU525, and MET388. The molecular docking study of these compounds indicated that chalcone 1 and pyridine 2 showed a promising anticancer effect.