43043-32-9Relevant articles and documents
Structural optimization and antibacterial evaluation of rhodomyrtosone B analogues against MRSA strains
Zhao, Liyun,Liu, Hongxin,Huo, Luqiong,Wang, Miaomiao,Yang, Bao,Zhang, Weimin,Xu, Zhifang,Tan, Haibo,Qiu, Sheng-Xiang
, p. 1698 - 1707 (2018)
Methicillin-resistant Staphylococcus aureus (MRSA) infections are well-known as a significant global health challenge. In this study, twenty-two congeners of the natural antibiotic rhodomyrtosone B (RDSB) were synthesized with the aim of specifically enhancing the structural diversity through modifying the pendant acyl moiety. The structure-activity relationship study against various MRSA strains revealed that a suitable hydrophobic acyl tail in the phloroglucinol scaffold is a prerequisite for antibacterial activity. Notably, RDSB analogue 11k was identified as a promising lead compound with significant in vitro and in vivo antibacterial activities against a panel of hospital mortality-relevant MRSA strains. Moreover, compound 11k possessed other potent advantages, including breadth of the antibacterial spectrum, rapidity of bactericidal action, and excellent membrane selectivity. The mode of action study of compound 11k at the biophysical and morphology levels disclosed that 11k exerted its MRSA bactericidal action by membrane superpolarization resulting in cell lysis and membrane disruption. Collectively, the presented results indicate that the novel modified RDSB analogue 11k warrants further exploration as a promising candidate for the treatment of MRSA infections.
Structure-activity relationships and optimization of acyclic acylphloroglucinol analogues as novel antimicrobial agents
Tan, Haibo,Liu, Hongxin,Zhao, Liyun,Yuan, Yao,Li, Bailin,Jiang, Yueming,Gong, Liang,Qiu, Shengxiang
supporting information, p. 492 - 499 (2016/10/04)
Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to global public health, because it exhibits resistance to existing antibiotics and therefore high rates of morbidity and mortality. In this study, twenty-one natural product-based acylphloroglucinol congeners were synthesized, which possessed different side chains. Antibacterial screening against MRSA strains revealed that acyl moiety tailoring is a prerequisite for the antibacterial activity. Moreover, the lipophilicity, rather than the magnitude of the hydrophobic acyl tail dominates variability in activity potency. Compound 11j was identified as a promising lead for the generation of new anti-MRSA drug development. It was discovered by optimization of the side chain length in light of the potency, the breadth of the antibacterial spectrum, the rate of bactericidal action, as well as the membrane selectivity. Compound 11j exerted profound in?vitro antibacterial activity against the MRSA strain (JCSC 2172), and its MIC was 3-4 orders of magnitude lower than that of vancomycin. A preliminary mode of action study of compound 11j at the biophysical and morphology levels disclosed that the mechanism underlying its anti-MRSA activity included membrane depolarization and, to a lesser extent, membrane disruption and cell lysis.
Antifungal Activities of 2,4,6-Trihydroxyacylophenones and Related Compounds
Mizobuchi, Shigeyuki,Sato, Yuko
, p. 719 - 724 (2007/10/02)
The antifungal activities of sixty two 2,4,6-trihydroxyacylophenones and related compounds against Trichophyton spp. and other fungi were investigated to study their structure-activity relationship.It was found that the activities of these compounds were closely related to the length of the acyl and alkyl chains attached to the 1,3,5-trihydroxybenzene moiety.Among the compounds tested, 2,4,6-trihydroxy-3-nonylacetophenone (V-7) showed the highest activity against Trichophyton spp., with MICs being 1.57 μg/ml, and was more active than amphotericin B.
