Synthesis, biological evaluation, quantitative-SAR and docking studies of novel chalcone derivatives as antibacterial and antioxidant agents

In the present study, a series of chalcone derivatives including 17 new compounds were synthesised; their antibacterial activities against eleven bacteria, and their free radical-scavenging activities using DPPH were evaluated. All compounds showed significant antibacterial activities against both Gram-positive and Gram-negative bacteria. In particular, compound IIIf strongly inhibited Staphylococcus aureus (JMC 2151) and Enterococcus faecalis (CARS 2011-012) with MIC values of 6.25 mu g mL(-1) and 12.5 mu g mL(-1), respectively, which are comparable to that of the standard antibiotic, nalidixic acid. Compound IIIg also inhibited S. aureus with a MIC value similar to that of nalidixic acid (6.25 mu g mL(-1)). Furthermore, like nalidixic acid (MIC value of 25 mu g mL (1)), compounds IIIa, IIIc and IIId inhibited Listeria monocytogenes (ATCC 43256) with MIC values of 25 mu g mL(-1), 12.5 mu g mL(-1) and 25 mu g mL(-1), respectively. Quantitative structure-activity relationship (Q-SAR) studies using physicochemical calculations indicated that the antibacterial activities of chalcone derivatives correlated well with predicted physicochemical parameters (logP and PSA). Docking simulation by positioning the most active compound IIIf in the active site of the penicillin-binding protein (PBP-1b) of S. aureus was performed to explore the feasible binding mode. Furthermore, most of the compounds synthesised exhibited significant DPPH radical-scavenging activity, although compounds IIc and IIIc exhibited the greatest antioxidant activity with IC50 values of 1.68 mu M and 1.44 mu M, respectively, comparable to that of the standard antioxidant, ascorbic acid (1.03 mu M). (C) 2015 Institute of Chemistry, Slovak Academy of Sciences