Known compounds and new lessons: structural and electronic basis of flavonoid-based bioactivities.

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. Abbreviations2'HFN-2'hydroxy flavonone2D2 dimension3D3 dimension3H7MF3-hydroxy-7-methoxy flavone4'HFN-4'hydroxy flavonone4'MF- 4'methoxy flavone7HFN7-hydroxy flavononeCHARMMChemistry at Harvard Macromolecular MechanicsCOXcyclooxygenaseCOX-1cyclooxygenase-1COX-2cyclooxygenase-2DMdipole momentDPPH- 2, 2diphenyl-1-picryl hydrazineEAelectron affinitiesEGFRepidermal growth factor receptorE-HOMOHighest occupied molecular orbital energyE-LUMOLowest unoccupied molecular orbital energyEPAeicosapentaenoic acidFROG2FRee Online druG conformation generationGAGenetic AlgorithmGROMACSGROningen MAchine for Chemical SimulationsHOMOHighest occupied molecular orbitalIPIonization potentialLOMOLowest unoccupied molecular orbitalMDMolecular dynamicsMOMolecular orbitalNAMDNanoscale Molecular DynamicsNSAIDsNon-Steroidal Anti Inflammatory DrugsNsnanosecondsNVEEnsemble-constant-energy, constant-volume, Constant particle ensemblePDB-IDProtein Data Bank IdentifierPMEParticle Mesh EwaldPyRXPython PrescriptionRMSDRoot-Mean-Square DeviationRMSFRoot-Mean-Square FluctuationRLSreactive lipid speciesROSReactive Oxygen SpeciesSASAsolvent accessible surface areaSMILESsimplified molecular-input line-entry systemSORsuperoxide anion radicalUFFUniversal force fieldVEGFvascular endothelial growth factorVEGFRvascular endothelial growth factor receptorVMDVisual molecular dynamicsCommunicated by Ramaswamy H. Sarma.

FlavoDb: a web-based chemical repository of flavonoid compounds.

There are many online resources that focus on chemical diversity of natural compounds, but only handful of resources exist that focus solely on flavonoid compounds and integrate structural and functional properties; however, extensive collated flavonoid literature is still unavailable to scientific community. Here we present an open access database 'FlavoDb' that is focused on providing physicochemical properties as well as topological descriptors that can be effectively implemented in deducing large scale quantitative structure property models of flavonoid compounds. In the current version of database, we present data on 1, 19,400 flavonoid compounds, thereby covering most of the known structural space of flavonoid class of compounds. Moreover, effective structure searching tool presented here is expected to provide an interactive and easy-to-use tool for obtaining flavonoid-based literature and allied information. Data from FlavoDb can be freely accessed via its intuitive graphical user interface made available at following web address: http://bioinfo.net.in/flavodb/home.html.