5665-89-4Relevant articles and documents
Synthesis and antibiotic activity of novel acylated phloroglucinol compounds against methicillin-resistant Staphylococcus aureus
Mittal, Navriti,Tesfu, Haben H.,Hogan, Andrew M.,Cardona, Silvia T.,Sorensen, John L.
, p. 253 - 259 (2019/02/19)
The rise in antibiotic resistance among pathogenic microorganisms has created an imbalance in the drugs available for treatment, in part due to the slow development of new antibiotics. Cystic fibrosis (CF) patients are highly susceptible to antibiotic-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Phloroglucinols and related polyketide natural products have demonstrated antimicrobial activity against a number of Gram-positive bacteria including S. aureus. In this study, we investigated a series of acylated phloroglucinol derivatives to determine their potential as lead compounds for the design of novel therapeutics. To assess the activity of these compounds, we determined the minimum inhibitory and bactericidal concentration (MIC and MBC, respectively), the minimum biofilm inhibitory and biofilm eradication concentration (MBIC and MBEC, respectively), and evaluated hemolytic activity, as well as their interaction with clinically relevant antibiotics. Of the 12 compounds tested against MRSA and methicillin-susceptible strains, four showed MIC values ranging from 0.125 to 8 μg ml?1 and all of them were bactericidal. However, none of the compounds were able to eradicate biofilms at the concentrations tested. Three of the four did not display hemolytic activity under the conditions tested. Further studies on the interactions of these compounds with clinically relevant antibiotics showed that phlorodipropanophenone displayed synergistic activity when paired with doxycycline. Our results suggest that these acylated phloroglucinols have potential for being further investigated as antibacterial leads.
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.
Cloning and structure-function analyses of quinolone- and acridone-producing novel type III polyketide synthases from citrus microcarpa
Mori, Takahiro,Shimokawa, Yoshihiko,Matsui, Takashi,Kinjo, Keishi,Kato, Ryohei,Noguchi, Hiroshi,Sugio, Shigetoshi,Morita, Hiroyuki,Abe, Ikuro
, p. 28845 - 28858 (2013/10/22)
Background:Type III polyketide synthases (PKSs) synthesize various polyketide and alkaloid scaffolds. Results:QNS synthesizes quinolone as the single product, whereas ACS produces acridone as the major product. Conclusion:QNS and ACS are novel quinolone- and acridone-producing type III PKSs, respectively. Significance:Structure-function analyses of QNS and ACS provide insights into molecular bases for alkaloid biosyntheses.
