70437-18-2Relevant academic research and scientific papers
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.
Compound, pharmaceutical composition, medicine and application of compound, pharmaceutical composition and medicine in preparation of antibacterial products
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, (2021/07/17)
The invention particularly relates to a compound, a pharmaceutical composition, a medicine and application of the compound, the pharmaceutical composition and the medicine in preparation of antibacterial products. The seeking of a novel antibacterial target and the development of a novel chemical entity have important significance for solving the increasingly severe bacterial drug resistance problem at present, and the design of a compound entity acting on the FtsZ target is expected to be developed to obtain an antibacterial drug which has no influence on a host. The invention provides a 9-aralkyl-10-methylacridine quaternary ammonium salt derivative and a preparation method thereof, and the compound has significant bactericidal and/or bacteriostatic activity on gram-positive bacteria, has a good effect of inhibiting bacterial division protein FtsZ, and can be used for preparing antibacterial products.
Arylethynylacridines: Electrochemiluminescence and photophysical properties
Elangovan, Arumugasamy,Chiu, Hsing-Hua,Yang, Shu-Wen,Ho, Tong-Ing
, p. 3113 - 3118 (2007/10/03)
Electrogenerated chemiluminescence (ECL) of six new ethyne-based acridine derivatives (1-6) has been studied. The new acridine derivatives were synthesized by cross-coupling of 9-chloroacridine and corresponding donor-substituted phenylethynes under modified Sonogashira conditions. The donor groups were varied in the order of increasing steric hindrance and donor strength at the donor site. The solution phase photophysical properties and ECL of these compounds were studied comparatively in acetonitrile solvent. The UV-Visible spectra of compounds 1-5 exhibit closely the same maxima. Density functional theory (DFT) has been invoked to analyze and understand the unexpected UV-Visible absorption behavior. Compounds with weak electron donors produce excimer ECL irrespective of steric hindrance at the donor site, while the compound with a stronger donor gives rise to ECL that is blue-shifted with respect to its photoluminescence spectrum. All except one of these compounds also exhibit solid state fluorescence which may be useful for solid state devices such as organic light emitting diodes (OLEDs) and as laser dyes. The observed properties are discussed with reference to the structure of the compounds synthesized.
