Design, Synthesis And Antibacterial Activity Research On Styrylimidazole Rersistance To Antibiotic Resistant Bacteria Active Compounds

The excessive use (and abuse) of antibiotics has played a critical causative role in the development of antibiotic resistance, which is now recognized as a global public health threat. In the company of an increase in the isolation of antibiotics-resistant strains, it will turn out ticklish aspect for general bacterial infection diseases and severer problems for clinical anti-infection treatment. Accordingly, the discovery of new effective drugs to counter the spread of antibiotic resistance has widely been paid attention, is aslo an urgent need. Based on the structures of A01, an anti-multidrug resistant Gram-positive bacterial compound we discovered before, for improving antibiotics activity and broadening antibacterial spectrum, we design several series of styrylimidazole compounds. Totally, fifty-three derivatives were synthesized (A02-54), including 314-substitued imidazole-containing novel derivatives (A21, A23-24 and A27-54). All compounds were assayed in seven clinic antibiotics-resistant strains (3 G+ and 4 G-). The results indicated that 31 compounds showed moderate antibiotics activities (MIC<32μg/mL in 3 G+),20 compounds showed potent antibiotics activities (MIC<10μg/mL in 3 G+), and 12 compounds showed very potent antibiotics activities (MIC≤2μg/mL in 3 G+). The most potent compounds is A30, with MIC values of 1,1,0.5μg/mL against 3 G+. It is noteworthy that derivative A12 shows, to a certain degree, broad-spectrum antibacterial property. Considering the simple stucture and big space for optimization of compound A12, it may serve as a reasonable lead compound for further developments. On the basis of biological results, we can deduce the preliminary structure-activity relationships (SARs) of these 54 compounds, which give some valuable clues for further design and development of new, broad-spectrum, anti-multidrug resistant bacterial agents.