Design, Synthesis And Antibacterial Activity Of FtsZ Inhibitors-3-MBA Derivatives

Bacterial drug resistance problem has posed severe threats to global public health, there is an urgent need to find effective ways to overcome the bacterial drug resistance. New targets and new skeleton antibacterial drugs are expected to solve this problem. Bacteria division is one of the most important life processes of bacterial proliferation. Filamentous temperature sensitive protein Z(Fts Z) is one of the key protein in the bacteria division. FtsZ assembles into ring-like structure that lies to the cytoplasmic membrane at the prospective division site, and then constrict the ring to give rise to two equal daughter cells. 3-Methoxybenzylamine(3-MBA) is a weak FtsZ protein inhibitor, and elongating alkyloxy can enhance its inhibition effect. According to the structure-activity relationship(SAR) of the 3-MBA, fluorine substituted 3-MBA was selected as a lead compound, various phenols and 8-hydroxyquinolines functional groups were introduced as a side chain via different linkers. Two series, a total of 22 goal of new compounds in series A and B, were designed and synthesized. The compounds were evaluated for the antimicrobial activity in vitro in the study. It was found that some compounds showed moderate antibacterial activity. Among them, A series compounds was active against gram positive bacteria, B series compounds showed weak activity on the gram-positive bacteria, gram-negative bacteria and fungi. Halogen atom and polarity of the side chain may improve the antibacterial activity and broad-spectrum properties.