Synthesis and bioactivity studies of flavonoid and its derivatives

Abstract

Flavonoids are the most widespread class of plants constituents. Most flavonoids are produced in biosynthetic pathways of secondary metabolites in plants and chalcones constituent as the important intermediate in flavonoid biosynthesis. In this study, eleven flavonoid derivatives were synthesized namely 2',3,4-trihydroxy-4',6'-dimethoxychalcone (110), 2',4',6'-trihydroxy-4,6-dimethoxychalcone (120), along with new compounds of 4',5,7-trimethoxy-3'-O-prenylflavanone (123), 4',5,7-trimethoxy-3'-O-6-C-diprenylflavanone (126), 2'-hydroxy- 4',6'- dimethoxy-3,4-methylenedioxy -3'-C-prenylchalcone (127), 5,6- chroman- 7-methoxy- 3',4'-methylenedioxyflavone (130), 5,6,7,8- dichroman- 3',4'- methylenedioxyflavone (132), 5',6'- chroman-2',3,4- trihydroxy- 4'-methoxychalcone (134), 3',4',5',6'-dichroman- 2',3,4-trihydroxychalcone (137), 3',4',5',6'-dichroman-3,4-dimethoxy-2'-hydroxychalcone (138) and 5',6'- chroman-2'- hydroxy-4'- methoxy-3,4-O-diprenylchalcone (139). The initial step in the synthesis was to prepare various derivatives of 2,4,6-trihydroxyacetophenone and 3,4-dihydroxybenzaldehyde by methylation, methylenation, protection and prenylation of the phenolic hydroxyl groups. The derivatives of both ketone and aldehyde were coupled and reacted using Claisen-Schmidt condensation to obtain the desired 2'-hydroxychalcone. 2'-Hydroxy-4,4',6'-trimethoxy-3-O-prenylchalcone (122) and 4,4',6'-trimethoxy-3-O-5'-C-diprenylchalcone (125) underwent an acid hydrolysis to yield flavanones (123) and (126), respectively. In addition, 2'-hydroxy- 4-methoxy- 5,6-chroman- 3,4-methylenedioxychalcone (129) and 2'- hydroxy- 3',4',5',6'- dichroman- 3,4-methylenedioxychalcone (131) were converted to flavones (130) and (132) using iodine in dimethylsulfoxide as an oxidative agent The structures of all compounds were confirmed spectroscopically by UV, IR, NMR and MS analysis. The biological studies of all the synthetic compounds were tested towards antioxidant, anti-inflammatory and antibacterial properties. The hydroxylated flavonoids with 3,4-dihydroxyl substituents were tested positive in 2,2-diphenyl-1-dipicrylhydrazyl (DPPH) assay and the highest antioxidant activity was exhibited by chalcone (110) with IC50 19.3 µg/mL. Two assays were used to evaluate the potential of the compounds as anti-inflammation agents. The results showed that chalcones (110) (IC50 2.4 µg/mL), (134) (IC50 1.94 µg/mL) and (137) (IC50 20.8 µg/mL) which possessed 3,4-dihydroxyl substituents exhibited good activity in the 13-lipooxygenase (LOX) assay. For xanthine oxidase assay, chalcone (120) with 4',6'-dihydroxyl showed a significant activity with IC50 6.83 µg/mL. All the synthesized flavonoids were found inactive towards the tested bacteria in the antibacterial assay.