Antimicrobial 3-methylene flavanones

Ward, Frederick E.; Garling, David L.; Buckler, Robert T.; Lawler, David M.; Cummings, Dennis P.

doi:10.1021/jm00141a011

Cited by 45 publications

(26 citation statements)

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“…This correlates well with previous work by Alcaraz et al who found that 4 -oxymethylflavanone had a MIC in excess of 1000 g/mL against S. aureus [52]. Older research, worth mentioning here because it corresponds well with recent data for the chalcones [47], indicates that bromo-(and chloro-) groups at positions 2 , 3 and 4 improve flavanone activity [41].…”

Section: Other Flavonoid Classessupporting

confidence: 91%

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Recent advances in understanding the antibacterial properties of flavonoids

Cushnie

Lamb

2011

International Journal of Antimicrobial Agents

1,020

672

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Antibiotic resistance is a major global problem and there is a pressing need to develop new therapeutic agents. Flavonoids are a family of plant-derived compounds with potentially exploitable activities, including direct antibacterial activity, synergism with antibiotics, and suppression of bacterial virulence. In this review, recent advances towards understanding these properties are described. Information is presented on the ten most potently antibacterial flavonoids as well as the five most synergistic flavonoid-antibiotic combinations tested in the last 6 years (identified from PubMed and ScienceDirect). Top of these respective lists are panduratin A, with minimum inhibitory concentrations (MICs) of 0.06-2.0 μg/mL against Staphylococcus aureus, and epicatechin gallate, which reduces oxacillin MICs as much as 512-fold. Research seeking to improve such activity and understand structure-activity relationships is discussed. Proposed mechanisms of action are also discussed. In addition to direct and synergistic activities, flavonoids inhibit a number of bacterial virulence factors, including quorum-sensing signal receptors, enzymes and toxins. Evidence of these molecular effects at the cellular level include in vitro inhibition of biofilm formation, inhibition of bacterial attachment to host ligands, and neutralisation of toxicity towards cultured human cells. In vivo evidence of disruption of bacterial pathogenesis includes demonstrated efficacy against Helicobacter pylori infection and S. aureus α-toxin intoxication.

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Section: Other Flavonoid Classessupporting

confidence: 91%

“…Synthetic modification of natural flavonoid structures has been reported as early as 1981 [41], but it is only in recent years that there has been a real surge of work in this area. Particularly successful alterations include linking an N-heterocyclic ring to the A ring of chrysin (position 7).…”

Section: Semisynthetic and Synthetic Flavonoidsmentioning

confidence: 99%

Recent advances in understanding the antibacterial properties of flavonoids

Cushnie

Lamb

2011

International Journal of Antimicrobial Agents

1,020

672

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“…1 and Table I). However, as also reported for a class molecules of close chemical structure (32), compounds with this structure are not stable at neutral pH, undergoing decomposition with t1 ⁄2 of ϳ30 min at pH 7.4. The corresponding enone decomposition product of Ro 04-2843, i.e.…”

Section: Screening and Identification Of A New Class Of Ptp Inhibitors-supporting

confidence: 59%

The Voltage-dependent Anion Channel Is the Target for a New Class of Inhibitors of the Mitochondrial Permeability Transition Pore

Cesura¹,

Pinard²,

Schubenel³

et al. 2003

Journal of Biological Chemistry

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The relevance of the mitochondrial permeability transition pore (PTP) in Ca 2؉ homeostasis and cell death has gained wide attention. Yet, despite detailed functional characterization, the structure of this channel remains elusive. Here we report on a new class of inhibitors of the PTP and on the identification of their molecular target. The most potent among the compounds prepared, Ro 68-3400, inhibited PTP with a potency comparable to that of cyclosporin A. Since Ro 68-3400 has a reactive moiety capable of covalent modification of proteins, [3 H]Ro 68-3400 was used as an affinity label for the identification of its protein target. In intact mitochondria isolated from rodent brain and liver and in SH-SY5Y human neuroblastoma cells, [ 3 H]Ro 68-3400 predominantly labeled a protein of ϳ32 kDa. This protein was identified as the isoform 1 of the voltage-dependent anion channel (VDAC). Both functional and affinity labeling experiments indicated that VDAC might correspond to the site for the PTP inhibitor ubiquinone 0 , whereas other known PTP modulators acted at distinct sites. While Ro 68-3400 represents a new useful tool for the study of the structure and function of VDAC and the PTP, the results obtained provide direct evidence that VDAC1 is a component of this mitochondrial pore.

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“…Although others have previously reported that several flavonoids posses antibacterial activity (Cai and Wu, 1996;el-Gammal and Mansour, 1986;Inamori et al, 1991;Ng et al, 1996;Osawa et al, 1992;Rocha et al, 1995;Ward et al, 1981;Zheng et al, 1996), to the best of our knowledge, this is the first report of a comprehensive examination of flavonoids within the seven structural classes for activity against drug-resistant bacteria. In particular, myricetin appears to possess broad-spectrum activity against grampositive (e.g.…”

Section: Resultsmentioning

confidence: 78%

“…Many flavonoids have been reported to possess a variety of biological activities including antiallergic, antiinflammatory, antiviral, antiproliferative and anticarcinogenic activities, in addition to having effects on mammalian metabolism (Middleton and Kandaswami, 1993). Although there were several earlier reports indicating the antibacterial activity of a few flavonoids (Cai and Wu, 1996;el-Gammal and Mansour, 1986;Inamori et al, 1991;Ng et al, 1996;Osawa et al, 1992;Rocha et al, 1995;Ward et al, 1981;Zheng et al, 1996), the antibacterial properties of flavonoids at large has not been investigated. Tsuchiya et al (1996) and Iinuma et al (1994) have reported that tetrahydroxyflavanones and exiguaflavanone D were active against MRSA, however, the activity of flavonoids against other antibiotic-resistant bacteria has not been examined.…”

Section: Introductionmentioning

confidence: 99%