Chemical reactivity of some isothiazolone biocides

Collier, Phillip J.; Ramsey, Andrew J.; Waigh, Roger D.; Douglas, Kenneth T.; Austin, P. W.; Gilbert, Peter

doi:10.1111/j.1365-2672.1990.tb01551.x

Cited by 126 publications

(98 citation statements)

References 8 publications

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“…The reactivity of isothiazolones with cysteine residues has been described previously. Isothiazolones have growth-inhibitory activity toward E. coli and Schizosaccharomyces pombe (44). The addition of a thiol-reducing agent quenched this effect.…”

Section: Discussionmentioning

confidence: 99%

Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity

Stimson

Rowlands

Newbatt

et al. 2005

Molecular Cancer Therapeutics

209

128

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Histone acetylation plays an important role in regulating the chromatin structure and is tightly regulated by two classes of enzyme, histone acetyltransferases (HAT) and histone deacetylases (HDAC). Deregulated HAT and HDAC activity plays a role in the development of a range of cancers. Consequently, inhibitors of these enzymes have potential as anticancer agents. Several HDAC inhibitors have been described; however, few inhibitors of HATs have been disclosed. Following a FlashPlate highthroughput screen, we identified a series of isothiazolonebased HAT inhibitors. Thirty-five N-substituted analogues inhibited both p300/cyclic AMP -responsive element binding protein -binding protein -associated factor (PCAF) and p300 (1 to >50 Mmol/L, respectively) and the growth of a panel of human tumor cell lines (50% growth inhibition, 0.8 to >50 Mmol/L). CCT077791 and CCT077792 decreased cellular acetylation in a time-dependent manner (2 -48 hours of exposure) and a concentration-dependent manner (one to five times, 72 hours, 50% growth inhibition) in HCT116 and HT29 human colon tumor cell lines. CCT077791 reduced total acetylation of histones H3 and H4, levels of specific acetylated lysine marks, and acetylation of A-tubulin. Four and 24 hours of exposure to the compounds produced the same extent of growth inhibition as 72 hours of continuous exposure, suggesting that growth arrest was an early event. Chemical reactivity of these compounds, as measured by covalent protein binding and loss of HAT inhibition in the presence of DTT, indicated that reaction with thiol groups might be important in their mechanism of action. As one of the first series of small-molecule inhibitors of HAT activity, further analogue synthesis is being pursued to examine the potential scope for reducing chemical reactivity while maintaining HAT inhibition. [Mol Cancer Ther 2005;4(10):1521 -32]

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Section: Discussionmentioning

confidence: 99%

Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity

Stimson

Rowlands

Newbatt

et al. 2005

Molecular Cancer Therapeutics

209

128

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“…While their primary action on the cell is mediated through a chemical interaction with thiols (57), specificity is seen towards a number of respiratory enzymes (56), and at sub-MIC levels, they have been shown to induce filamentation both in bacteria and in the fission yeast Schizosaccharomyces pombe (55). While lethal doses affect thiol groups on proteins, sublethal doses more specifically affect DNA (57,93). Phenylethanol is also known to inhibit the initiation of DNA replication and to cause a filamentation similar to that caused by the isothiazolones (267).…”

Section: Biocide Action Mechanismmentioning

confidence: 99%

Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance

2003

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There has recently been much controversy surrounding the increased use of antibacterial substances in a wide range of consumer products and the possibility that, as with antibiotics, indiscriminate use of biocides might contribute to the overall pattern of susceptibility in the general environment and in the clinic. Such speculation, based on the isolation of resistant mutants from in vitro monoculture experiments, is not reflected by an emergence of biocide-resistant strains in vivo. This review provides a broad coverage of the biocide and resistance literature and evaluates the potential risks, perceived from such laboratory monoculture experiments, against evidence gathered over 50 years of field studies. An explanation for the continued effectiveness of broad-spectrum biocidal agents against the decline in efficacy of therapeutic agents is provided based on the fitness costs of resistance and the ubiquity of naturally occurring substances that possess antibacterial effect. While we conclude from this review of the literature that the incorporation of antibacterial agents into a widening sphere of personal products has had little or no impact on the patterns of microbial susceptibility observed in the environment, the associated risks remain finite. The use of such products should therefore be associated with a clear demonstration of added value either to consumer health or to the product life. Hygienic products should therefore be targeted to applications for which the risks have been established

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“…Sea-Nine 211 ® has a broad spectrum activity (e.g. against fungi, algae, bacteria and marine invertebrates) and reacts with thiol-containing enzymes (Collier et al 1990). Zinc pyrithione inhibits bacterial ATP synthesis and membrane transport (Dinning et al 1998) and generates hydroxyl radicals when photolysed with visible or UV light (Aveline et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Impact of antifouling booster biocides on single microalgal species and on a natural marine phytoplankton community

Devilla¹,

Brown²,

Donkin³

et al. 2005

Mar. Ecol. Prog. Ser.

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Chemical reactivity of some isothiazolone biocides

Cited by 126 publications

References 8 publications

Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity

Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity

Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance

Impact of antifouling booster biocides on single microalgal species and on a natural marine phytoplankton community

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