Design Synthesis and Pharmacological Screening of Novel Flavonols

Abstract

Flavonols are a class of privileged structures that display a remarkable newlinespectrum of biological activities. The objective of present research work was to newlinedesign and synthesize different derivatives of naturally occurring flavonols with the newlineaim that the synthesized derivatives have more potential pharmacological activities newlinethan the naturally occurring ones. Accordingly the flavonol derivatives to be newlinesynthesized were designed and docked onto the selected protein template viz. newlineHaematopoietic cell kinase (PDB ID: 1QCF) for anticancer activity and Asparaginyl newlinetRNA synthetase (PDB ID: 4ZYA) for antifilarial activity to determine the binding of newlinedesigned compounds with the protein structure using Schrodinger Autodock 4.2 newlinesoftware. Next the compounds with greater binding affinity with target proteins were newlinesynthesized by Claisen-Schmidt condensation of substituted 2-hydroxy acetophenones newlinewith substituted aromatic aldehydes using polyethylene glycol-400 to form 2-hydroxy newlinechalcones. Later the title flavonols were synthesized by an Algar Flynn Oyamada newlinemethod which includes oxidative cyclization of 2-hydroxy chalcones in basic solution newlineby hydrogen peroxide. The reaction led to the expected products with high yield and newlinein almost all cases the products obtained in pure form. The synthesized derivatives newlinewere identified by different chemical tests and characterized by different newlinephysicochemical parameters like melting point, TLC, Rf value and spectral newlineparameters like IR, 1H-NMR, mass and elemental analysis. The characterization data newlineconfirmed the structures of final compounds. The synthesized compounds were newlineevaluated for in vitro anticancer activity on HL60 cell lines of human promyelocytic newlineleukemia by MTT assay. From the activity data, it is observed that the compound D22 newlinepossess highest activity amongst all the tested compounds. The selected compounds newlinewere screened for in vitro antifilarial activity on Brugia malayi parasite using newlineDiethylcarbamazine as standard. In this screening the negative results were obtained newlinewhich may be du