Optimizing and analysing the anti-cancer potential of novel quinoline acetohydrazide (QAH): A comprehensive study involving synthesis, structural evaluation, 3D energy frameworks, DFT calculations, in vitro and in silico evaluation

The compound, 2-(4-Chlorophenyl)-N'-(2-(quinoline-8-yloxy)acetyl acetohydrazide (QAH3), was synthezised in good yield from 2-(Quinoline-8-yloxy)acetohydrazide (1), with 2-(4-Chlorophenyl)acetic acid (2). The crude product obtained was recrystallized and elucidated by spectroscopic techniques (IR, HNMR and LC-MS), the 3D structure was confirmed by single crystal X-ray diffraction (XRD) studies. The XRD analysis shows that the compound crystallizes in the monoclinic crystal system with the space group Cc. Supramolecular architecture revealed the stability of molecules and crystal packing upon N-H...O, C-H...O, and C-H...pi interactions. The threedimensional Hirshfeld surfaces associated with two-dimensional fingerprint plots have confirmed the N-H...O, CH...O intermolecular interactions. An energy framework calculation is used to estimate the different intermolecular interactions where dispersion energy dominates over all others. The Egap found to be 4.478 eV and related reactivity parameters of the compound were studied. In vitro studies confirmed that QAH3 significantly inhibited vascular endothelial growth factor receptor II (VEGFR-2) with an IC50 value of 10.54 +/- 0.12 mu M, compared to quercetin, the pharmaceutical reference standard, which demonstrated an IC50 of 4.50 +/- 0.05 mu M. Furthermore, the anti-cancer activity was confirmed by an in silico modelling study that targeted the angiogenesis of the VEGFR-2 receptor with good a binding affinity of -9.43 kcal/mol. This research not only propels molecular science forward but also offers potential for diverse applications, especially in drug design. The study's significance lies in its comprehensive exploration of the pharmacological potential of Quinoline Acetohydrazide using a multidisciplinary approach. We have extensively investigated the structural and biological properties of these molecules by combining synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) computations. This investigation has provided valuable insights that could lead to significant advancements in molecular science and drug development. Noncovalent interactions study shows the steric and van der Waals interactions exist between chlorobenzene and quinoline rings. MEP analysis shows that the chemical reactive sites are observed around oxygen and hydrogen atoms. Moreover, the molecular docking investigations elucidate the compound's interaction with several biological targets. The significant binding affinities observed for these targets highlight the potential therapeutic relevance of the synthesized compound in treating diverse diseases.