Synthesis, QSAR analysis and mechanism of antybacterial activity of simple 2 '-hydroxy chalcones

Abstract

Twelve 2'-hydroxy chalcones were synthesized and their in vitro antibacterial activity was tested using eight standard strains of bacteria: S. aureus (ATCC 25923), S. epidermidis (ATCC 12228), B. subtilis (ATCC 6633), M. luteus (ATCC 10240), M. flavus (ATCC 9341), E. faecalis (ATCC 29212), K. pneumoniae (NCIMB 9111) and P. aeruginosa (ATCC 27853). All 2'-hydroxy chalcones have shown moderate to good antimicrobial activity, determined by microdilution method. QSAR analysis was performed for all the cases, R-2 = 0.918 - 0.997. The results of our QSAR analysis indicate that an alternative and complementary mechanism of action is a major determinant of 2'-hydroxy chalcone antibacterial efficiency. These chalcone derivatives posses the ability to act as bidendate chelating agents whereby the ketone moiety forms a coordinate bond and the 2'-hydroxy group forms a covalent bond with a corresponding metal ion. Chelate formation can disrupt the function of bacterial metalloproteins wich may affect the further growth of bacterial cells.