Synthesis, Characterization and Molecular Docking of New Naphthalene-Based Chalcone and Pyrazoline Compounds

Abstract

Most chemotherapeutic drugs are unable to distinguish between healthy and cancerous cells, resulting in the risk of side effects and drug resistance. There is a continuous effort to find new agents to help bring this disease under control. Compounds with bioactive natural product scaffolds have been of great interest due to their low toxicity and high efficacy. In this study, new naphthalene-based chalcone 1 and pyrazoline 1A compounds were synthesized via a Claisen-Schmidt condensation and cyclo-condensation reaction, respectively. These compounds were characterized using the Fourier Transform Infrared (FT-IR), 1H, and 13C Nuclear Magnetic Resonance (NMR) spectroscopy. The molecular docking activities were performed to study the interactions between these new compounds with breast cancer protein, 3ERT as estrogen receptor-α (ERα). Chalcone 1 and pyrazoline 1A compounds obey Lipinski's rule whereby pyrazoline 1A showed the lowest binding energy of -9.47 kcal/mol, inhibition constant of 113.93 mM and log P of 2.30. Interaction of pyrazoline 1A with 3ERT protein exhibited the hydrogen bonding with GLY521 amino acid, while the hydrophobic interactions were observed with LEU346, LEU384, LEU391, LEU525, LEU387, MET343, ALA350, and MET421 amino acids. Pyrazoline 1A is expected to show promising activities as an anticancer agent.