Synthesis, crystal structure, DFT calculations, Hirshfeld surface analysis, energy frameworks, molecular dynamics and docking studies of novel isoxazolequinoxaline derivative (IZQ) as anti-cancer drug

Abstract Quinoxaline derivatives with the molecular formula [C8H6N2] also named benzopyrazines, which are a valuable class of heterocyclic compounds useful for their numerous industrial and pharmaceutical applications. The new isoxazolquinoxalin (IZQ) 3-phenyl-1-((3-(p-tolyl)-4,5-dihydroisoxazol-5yl)methyl)quinoxalin-2(1H)-one (5) has been synthesized with good yield by stirring the compounds of 1-allyl-3-phenylquinoxalin-2(1H)-one (3, 3.8mmol), and (E)-4 methylbenzaldehydeoxime (4, 1.3mmol) in 20 ml of chloroform. The aqueous solution of sodium hypochlorite (10 ml of water bleach 12°) was added drop wise using bromine funnel. The mixture was stirring at 0°C temperature for 6 hours. Then it dried to obtain a crude product which on recrystallization with ethanol afforded the title compound (5) as colourless rectangular block shape crystals, and then confirmed by H NMR, LC-MS spectra. The structure of the compound has been confirmed by single crystal X-ray diffraction technique. The compound crystallizes in the monoclinic crystal system with the space group P21/c. The unit cell constants; a =15.9437(6) A, b =16.3936(6) A, c =7.4913(3) A, and β =94.178(2)o. DFT calculations were carried out and HOMO-LUMO energy levels have been determined. In the structure, both Intermolecular and intramolecular hydrogen bonds of the type C-H...O were observed along with C-H...cg interactions. Hirshfeld surface studies were performed to understand the different interaction contacts of the molecule and the molecular packing strength of the crystal. Energy frameworks were constructed through different intermolecular interaction energies to investigate the stability of the compound and to know type of the dominate energy. Docking studies predicted anti-cancer activity of the title molecule against homo sapiens protein (pdb code:6HVH) and exhibited prominent interactions at active site region.