Molecular docking, bioactivity, adme, toxicity risks, and quantum mechanical parameters of some 1,2dihydroquinoline derivatives were calculated theoretically for investigation of its use as a pharmaceutical active ingredient in the treatment of multiple sclerosis (MS)

Abstract

In this study, some 1,2-dihydroquinoline derivatives, which have not been synthesized before, were designed, and their usability in the treatment of multiple sclerosis (MS) was investigated. Firstly, a docking study was conducted between the designed molecules and the target proteins (3PP4, 6OBD, 7YXA, and 7TD4) that interact with drugs (International Nonproprietary Name (INN): Ocrelizumab, Alemtuzumab, and Siponimod) used in the treatment of MS. ADME (absorption, distribution, metabolism, and excretion) properties (Boiled Egg graph, bioavailability radar, physicochemical properties, lipophilicity, water solubility, pharmacokinetics, drug similarity, and medicinal chemistry) were analyzed. Bioactivity score, drug-likeness score, drug score, toxicity risks (mutagenic, tumorigenic, irritant, reproductive effective, fathead minnow LC50 (96 hours), daphnia magna LC50 (48 hours), oral rat LD50), bioconcentration factor, and density values were calculated. Quantum mechanical parameters include highest occupied molecular orbital energy (EHOMO), lowest unoccupied molecular orbital energy (ELUMO), chemical potential (mu), electron affinity (EA), global softness (S), global hardness (eta), ionization potential (IP), total energy, dipole moments, and electrophilicity (omega) values were also calculated for all molecules. As a result of the data obtained from all these studies, (7-(diethylamino)-1,2-dihydroquinolin3-yl)(6-(diethylamino)-2,3-dihydro-1H-indazol-1-yl)methanone was determined to be the most ideal molecule that can be used as a pharmaceutical active ingredient in the treatment of MS. Bond angles, bond lengths, Mulliken atomic charges, and molecular electrostatic potential (MEP) were calculated for this ideal molecule, and the structure of the molecule was explained in a multifaceted way.