Known compounds and new lessons: structural and electronic basis of flavonoid-based bioactivities. Issue 4 (3rd March 2020)

• Record Type: Journal Article
• Authors: Meshram, Rohan J.; Bagul, Kamini T.; Pawnikar, Shristi P.; Barage, Sagar H.; Kolte, Baban S.; Gacche, Rajesh N.
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 38:Issue 4(2020)
• Page Start: 1168
• Page End: 1184
• Publication Date: 2020-03-03
• Subjects: Flavonoids -- COX-2 inhibition -- HOMO -- LUMO -- dipole moment -- ionization potential -- molecular dynamics simulations; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2019.1597770
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: Flavonoids correspond to a major class of polyphenolic phytochemicals with flavone as major parent scaffold. This class of compounds is attributed with very rich nutritional as well as therapeutic values. The present study focuses on a panel of 16 flavonoid molecules that are demonstrated to exhibit various bioactivities like anti-angiogenic, anti-inflammatory as well as possess antioxidant potential. The electronic basis of these bioactivities is rarely explored, and structural basis of flavonoid-induced cyclooxygenase (COX) inhibition has still remained an uncharted area. The current report thus focuses on providing an electronic explanation of these bioactivities using density functional theory-based quantum chemical descriptors. We also attempt to provide a structure–activity relation model for COX by inhibition of these 16 flavonoids using molecular docking. Here, we report molecular dynamics data from 16 flavonoid–COX-2 complexes performed for 50 nanoseconds each that demonstrates key structural and dynamic aspects of flavonoid-based COX inhibition in light of observed experimental facts. Interaction analysis and evaluation of side-chain dynamics presented in current study are well in agreement with the empirical study and is hoped to pave new avenues towards design and development of COX-2 selective chemical agents. Abbreviations: 2′HFN-2′ hydroxy flavonone 2D 2 dimension 3D 3 dimension 3H7MF 3-hydroxy-7-methoxy flavone 4′HFN-4′ hydroxy flavonone 4′MF- 4′ methoxy flavone 7HFN 7-hydroxy flavonone CHARMM Chemistry at Harvard Macromolecular Mechanics COX cyclooxygenase COX-1 cyclooxygenase-1 COX-2 cyclooxygenase-2 DM dipole moment DPPH- 2, 2 diphenyl-1-picryl hydrazine EA electron affinities EGFR epidermal growth factor receptor E-HOMO Highest occupied molecular orbital energy E-LUMO Lowest unoccupied molecular orbital energy EPA eicosapentaenoic acid FROG2 FRee Online druG conformation generation GA Genetic Algorithm GROMACS GROningen MAchine for Chemical Simulations HOMO Highest occupied molecular orbital IP Ionization potential LOMO Lowest unoccupied molecular orbital MD Molecular dynamics MO Molecular orbital NAMD Nanoscale Molecular Dynamics NSAIDs Non-Steroidal Anti Inflammatory Drugs Ns nanoseconds NVE Ensemble-constant-energy, constant-volume, Constant particle ensemble PDB-ID Protein Data Bank Identifier PME Particle Mesh Ewald PyRX Python Prescription RMSD Root-Mean-Square Deviation RMSF Root-Mean-Square Fluctuation RLS reactive lipid species ROS Reactive Oxygen Species SASA solvent accessible surface area SMILES simplified molecular-input line-entry system SOR superoxide anion radical UFF Universal force field VEGF vascular endothelial growth factor VEGFR vascular endothelial growth factor receptor VMD Visual molecular dynamics Communicated by Ramaswamy H. Sarma