132058-87-8Relevant articles and documents
Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents
Song, Di,Zhang, Nan,Zhang, Panpan,Zhang, Na,Chen, Weijin,Zhang, Long,Guo, Ting,Gu, Xiaotong,Ma, Shutao
, (2021/05/10)
With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. In particular, the most promising compound 15f showed rapid bactericidal properties, which avoid the emergence of drug resistance. However, 15f showed no inhibitory effect on Gram-negative bacteria but biofilm formation study gave possible answers. Further target identification and mechanistic studies revealed that 15f functioned as an effective FtsZ inhibitor to alter the dynamics of FtsZ self-polymerization, which resulted in termination of the cell division and caused cell death. Further cytotoxicity and animal studies demonstrated that 15f not only displayed efficacy in a murine model of bacteremia in vivo, but also no significant hemolysis to mammalian cells. Overall, this compound with novel skeleton could serve as an antibacterial lead of FtsZ inhibitor for further evaluation of drug-likeness.
Regioselective C-H bond functionalizations of acridines using organozinc reagents
Hyodo, Isao,Tobisu, Mamoru,Chatani, Naoto
supporting information; experimental part, p. 308 - 310 (2012/01/05)
Despite the recent advance in C-H bond functionalization chemistry, the C-H bonds in the acridine ring system, which is an important scaffold in medicinal and material science, have met with limited success, due, in part, to the lack of activated C-H bonds adjacent to the ring nitrogen atom. Herein, several protocols that can effect the regioselective arylation and alkylation of acridines at the C-4 and C-9 positions are described.
