Molecular modeling, DFT studies and biological evaluation of methyl 2,8-dichloro-1,2-dihydroquinoline-3-carboxylate

Abstract

The need for Novel antimicrobial drugs aim at combating the essential elements of bacterial metabolism including cell walls, DNA gyrase, DNA-directed RNA polymerase, protein synthesis, and enzymes is very imperative considering the vast resistant of microbes and bacteria to modern drugs. This study looks at the evaluation of the biological activity and density functional theory (DFT) calculations of methyl 2,8-dichloro-1,2-dihydroquinoline-3-carboxylate (CMDP 2) in order to ascertain its usefulness in antibacterial therapy. The frontier molecular orbitals (FMO), Density of state (DOS), and natural bond orbital (NBO) were investigated using DFT at 6-311++G(d,p) basis set with different functionals (ωB97XD, TPSSTPSS and PBEPBE) for the elucidation of the molecular structural properties of the title molecule. Notably, the experimental and theoretical reported wavelength of absorption of the respective functional group are in good agreement. CMDP 2 shows highest interaction with ωB97XD functional. The investigated compounds' lowest binding energies ranged from −6 to −7 Kcal/mol, with CMPD 2 (−7 Kcal/mol) producing the best binding pose in its interaction with amino acid residues of 2NCJ, 5BS3 and 6RKU which is a satisfactory antibacterial property compared to 2-chloroquinoline-3-carbaldehyde (CMPD 1). CMPD 2 was also found to be both a non-substrate and non-inhibitor of CYP3A4 and CYP2D6 in the analysis, suggesting that the compound could be metabolized in the liver. CMDP 2 could serve as a good starting material for the development of further therapeutically effective antibacterial drugs.

Keywords

• Antibacteria
• DFT
• Molecular docking
• ADMET
• Quinoline