Synthesis And Antibacterial And PTP1B Inhibitory Activity Evaluation Of Rhodanine Derivatives

Nowadays,the abuse of antibiotics leads to the frequent occurrence of bacterial resistance,and the emergence of super bacteria invalidates most of the antibacterial drugs.Therefore,the search for new antibacterial drugs are an important part of the pharmaceutical work.Rodentane compounds have attracted much attention because they are physiologically active compounds with a wide range of biological activities,including antibacterial,anti-tumor,hypoglycemic and anti-convulsions.According to the previous work of the laboratory,a large number of rhodanine derivatives with excellent antibacterial activity have been synthesized and identified.Based on the analysis of structure-activity relationship(SAR)of rodentane derivatives,27 compounds were designed and synthesized,in which the naphthalene ring has been the model compound and some modifications were made at the 2-and 6-position of naphthalene ring by introducing substituted benzyl groups and various substituted rhodanine acetic acids,respectively.In this paper,the structures of all synthesized compounds were characterized by 1H NMR,13C NMR and HR-MS.All compounds were evaluated their antibacterial activity and four compounds were evaluated their PTP1B inhibitory activity.The antibacterial activity results revealed that the majority of the synthesized compounds showed potent inhibitory activity against the tested strains.Compound 4h displayed a good antibacterial activity with a MIC of 1 p.g/mL against S.aureus 4220.Compounds 7b and 7c showed inhibitory effect with a MIC of 1?g/mL against Streptococcus mutans 3289.Compounds 4d and 7c showed inhibitory effect with a MIC of 1?g/mL against Escherichia coli 1924.Compound 5d showed inhibitory effect with a MIC of 1?g/mL against Candida albicans 7535.All of the synthesized compounds were also tested for their inhibitory activities against the clinical isolates of several different multidrug-resistant Gram-positive bacterial strains.Compounds 4d,4e,4f,4h,6a,6f,7c and 7d with MIC values of 2 ?g/mL were as active as the standard drug Gatifloxacin and better active than Norfloxacin against QRSA 3505 and 3519.Compounds 4d,7b and 7c,with a MIC of 1?g/mL against MRSA 3167,showed eight-fold more potency than norfloxacin;Compounds 4a?4d?4e?4h?6a?6d?7c and 7d showed inhibitory activity with MIC values of 2 ?g/mL against MRSA 3506.In addition,four compounds were measured their PTP1B inhibitory activity and identified as reversible and competitive PTP1B inhibitors.Compound 4fhad the most potent in vitro inhibition activity against PTP1B(IC50 = 0.36±0.02?M).These compounds exhibited broad spectrum of antibacterial activity and potent PTP1B inhibitory activity.The results will provide experimental and theoretical clues for designing of novel potent antibacterial agents and PTP1B inhibitors.