Synthesis and biological evaluation of flavonoids as antimicrobial and antiacetylcholinesterase agents

Abstract

Flavonoids are polyphenolic compounds that are abundant in nature and are widely recognized for their antimicrobial, antioxidant, antimalarial, cytotoxic, antidepressant, anti-inflammatory and anticancer activity. In this research, synthesis of seven substituted chalcones, a flavone and flavanone were studied. The flavone and flavanone were synthesized via oxidative cyclization of the key intermediate, 2’- hydroxychalcone. To get the desired prenylated substitution pattern, 2,4-dihydroxy acetophenone and dimethylallyl bromide were subjected to prenylation process in the presence of DBU and THF to afford 2-hydroxy-4-O-prenyl- acetophenone. The 2- hydroxy-4-O-prenylacetophenone, 2-hydroxyacetophenone and 4-hydroxyaceto phenone underwent Claisen-Schmidt condensation with benzaldehyde derivatives under basic media to acquire 2’-hydroxy-4-chlorochalcone, 2’-hydroxy-4-nitro chalcone, 2’-hydroxy-4-(dimethyl)aminochalcone, 2’-hydroxy-4-methoxychalcone, 4’-hydroxy-2,6-dichlorochalcone 2’-hydroxy-4-O-prenyl-2,6-dichlorochalcone and 2’-hydroxy-2,6-dichlorochalcone. Using iodine in dimethyl sulfoxide as an oxidative agent, 2’-hydroxy-2,6-dichlorochalcone was cyclized to 2’6’-dichloroflavone. Furthermore, the 2’-hdroxy-2,6-dichlorochalcone reacted with sodium acetate in methanol to afford 2’,6’-dichloroflavanone. All structures were confirmed by spectroscopic methods which include; infrared (IR) and nuclear magnetic resonance (NMR) as well as physical data which were compared with the literatures. The biological properties, specifically antimicrobial and acetylcholinesterase inhibitory activities were tested for all the target compounds. 2’-Hydroxy-4-chlorochalcone and 2’-hydroxy-4-nitrochalcone displayed moderate antimicrobial activity against the Gram-positive bacteria with minimum inhibitory concentration (MIC) 125 µg/mL and weak activity against the Gram-negative bacteria and fungi with MIC 500 and 250 µg/mL, respectively. As for the acetylcholinesterase inhibition property, only 2’- hydroxy-4-methoxychalcone and 2’-hydroxy-4-O-prenyl-2,6-dichlorochalcone showed moderate activity with a detection limits of 0.1 and 0.23 mM respectively. The microplate assay showed that 4’-hydroxy-2,6-dichlorochalcone, 2’-hydroxy-4- nitrochalcone, 2’-hydroxy-4-(dimethyl)aminochalcone and 2’-hydroxy-4-methoxy chalcone displayed moderate AchE inhibitory activity with higher percentage inhibition of 54.24%, 44.22% and 52.39% and 46.36%, 40.14% respectively.