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

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-pheny1-14(3-(p-toly1)-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 degrees) was added drop wise using bromine funnel. The mixture was stirring at 0 degrees 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 P2(1)/c. The unit cell constants; a =15.9437(6) angstrom, b =16.3936(6) angstrom, c =7.4913(3) angstrom, and beta =94.178(2)degrees. 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 center dot center dot center dot O were observed along with C-H center dot center dot center dot 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. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

Quinoxaline derivatives, also known as benzopyrazines, are a valuable class of heterocyclic compounds with wide industrial and pharmaceutical applications. The synthesis of a new isoxazolquinoxalin compound and its crystal structure analysis revealed potential anti-cancer activity and various interaction contacts within the crystal lattice, demonstrating its stability and dominant energy type.