Structural and theoretical exploration of a multi-methoxy chalcone: Synthesis, quantum theory, electrostatics, molecular packing, DFT analysis, and in-silico anti-cancer evaluation

• Published in: Heliyon 2024-07, Vol.10 (13), p.e33814, Article e33814
• Main Authors: Al-Ostoot, Fares Hezam, Akhileshwari, P., Kameshwar, Vivek Hamse, Geetha, D.V., Aljohani, Majed S., Alharbi, Hussam Y., Khanum, Shaukath Ara, Sridhar, M.A.
• Format: Article
• Language: English
• Subjects: Anti-cancer activity; Chalcone; DFT calculations; Molecular electrostatic; Molecular packing; Quantum theory
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e33814

This study explores the pharmacological potential of chalcones through a multidisciplinary approach, including synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) calculations. The synthesized compound, analyzed via single crystal X-ray diffraction, crystallized in the triclinic system (space group P-1) with C–H⋯O interactions stabilizing its structure. Hirshfeld surface analysis confirms these interactions, with H–H contacts dominating (45.1 %). Molecular electrostatics analysis reveals charge distribution, and a 3.10 eV HOMO-LUMO energy gap indicates bioactivity. Molecular docking identifies the compound (3a) showed a maximum Gscore of HTNF-α (−9.81 kcal/mol); Tubulin (−7.96 kcal/mol); COX2 (−7.88 kcal/mol), EGFR (−6.72 kcal/mol), and VEGFR1(-2.50 kcal/mol). Where compound (3c) showed maximum binding at the putative binding site with dock scores for VEGFR2 (−9.24 kcal/mol). This research not only advances molecular science but also holds promise for diverse applications, including drug design. The significance of this study lies in its comprehensive exploration of the pharmacological potential of chalcones using a multidisciplinary approach. Through the integration of synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) calculations, we have extensively explored the structural and biochemical characteristics of these compounds. This investigation has revealed valuable insights that have the potential to lead to significant advancements in the fields of molecular science and drug design. Moreover, the molecular docking studies shed light on the compound's interaction with various biological targets. The significant binding affinities observed for these targets underscore the potential therapeutic relevance of the synthesized compound in diverse disease conditions. •Synthesis and structural analysis of a multi-methoxy chalcone analog.•Quantum theory, molecular electrostatics analysis, and the behaviors of the synthesized molecule.•Single crystal X-ray diffraction analysis, and DFT calculations.•Hirshfeld surface analysis, molecular packing analysis, and supramolecular assembly.•Molecular docking investigation of the target ligand as a highly promising VEGFR-2 inhibitor.