Synthesis and characterization of a new flavonoid derivative that inhibits KAS III enzyme and evaluation of its antibacterial activity

Abstract

Background and aim: Bacterial resistance has become an important topic that concerns many health organizations in general and the World Health Organization in particular. Therefore, it was necessary to find new antibacterial drug groups that do not have bacterial resistance, as antibiotics of natural origin are an important starting point for developing and designing new antibiotics that are highly effective in combating various bacterial infections, especially resistant ones. Flavonoid derivatives, the most important of which is chrysin, are one of the most promising products that can be used to develop new antibiotics that do not have bacterial resistance.

Materials and Methods: In this research, computer simulations were carried out on the KAS III (Fab H)enzyme using a new flavonoid derivative (chrysin acetate), which was synthesized through the esterification reaction of the phenolic function at position 7 in the chrysin structure. To achieve the computer simulations, X-ray crystal structures of the enzyme were used on the proteins IHNJ.pdb and 6KVS.pdb from Escherichia coli and Staphylococcus aureus. After that, work was done on the synthesis of the target derivative (chrysene acetate) based on chrysene by reacting it with acetic anhydride in a medium of acetone by heating. The target compound was obtained as a yellow precipitate, which was purified by repeated crystallization, and its structure was described using optical absorption spectroscopy. In the field of infrared, visible, ultraviolet, and proton and carbon nuclear magnetic resonance spectroscopy. Its biological effectiveness was later tested on Escherichia coli and Staphylococcus aureus bacteria.

Conclusion: Adding an acetate group to carbon atom 7 in chrysin structure leads to increase antibacterial activity.