2999-18-0Relevant articles and documents
Total synthesis and structure elucidation of (±)-triumphalone and (±)-isotriumphalone
Nishimura, Eiji,Ohfune, Yasufumi,Shinada, Tetsuro
, p. 539 - 541 (2015)
The first total synthesis of (±)-triumphalone has been achieved in 8 steps from phloroglucinol. Synthetic triumphalone was converted to (±)-isotriumphalone in one step by the α-ketol rearrangement in a highly efficient manner. Although NMR data of the syn
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.
Hits-to-lead optimization of the natural compound 2,4,6-trihydroxy-3-geranyl-acetophenone (thga) as a potent lox inhibitor: Synthesis, structure-activity relationship (sar) study, and computational assignment
Ng, Chean Hui,Rullah, Kamal,Abas, Faridah,Lam, Kok Wai,Ismail, Intan Safinar,Jamaludin, Fadzureena,Shaari, Khozirah
, (2018/10/15)
A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues 4a-g (half maximal inhibitory concentration (IC50) values ranging from 35 μM to 95 μM) did not exhibit better inhibitory activity than tHGA (3a) (IC50 value: 23.6 μM) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced. One geranylated analogue, 3d, with an IC50 value of 15.3 μM, exhibited better LOX inhibitory activity when compared to tHGA (3a), which was in agreement with our previous findings. Kinetics study showed that the most active analogue (3e) and tHGA (3a) acted as competitive inhibitors. The combination of in silico approaches of molecular docking and molecular dynamic simulation revealed that the lipophilic nature of these analogues further enhanced the LOX inhibitory activity. Based on absorption, distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction by komputer assisted technology (TOPKAT) analyses, all geranylated analogues (3a-g) showed no hepatotoxicity effect and were biodegradable, which indicated that they could be potentially safe drugs for treating inflammation.
