Mutagenicity of N-acylglycinohydroxamic acids and related compounds.

Munakata, Keiichi; Mochida, Hisatoshi; Kondo, S.; Suzuki, Yoshikazu

doi:10.1248/bpb1978.3.557

Cited by 22 publications

(8 citation statements)

References 13 publications

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“…• Reduction of the adhesion • Clinical study in progress Hydroxamic acid (Griffith et al, 1978(Griffith et al, , 1988(Griffith et al, , 1991Munakata et al, 1980;Bailie et al, 1986;Benini et al, 2000;Amtul et al, 2002;Xu et al, 2017) • Prevent urine alkalization • Prevent the formation of urinary stones…”

Section: Small Compoundsmentioning

confidence: 99%

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Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

et al. 2020

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Urinary tract infections (UTIs) mainly caused by Uropathogenic Escherichia coli (UPEC), are common bacterial infections. Many individuals suffer from chronically recurring UTIs, sometimes requiring long-term prophylactic antibiotic regimens. The global emergence of multi-drug resistant uropathogens in the last decade underlines the need for alternative non-antibiotic therapeutic and preventative strategies against UTIs. The research on non-antibiotic therapeutic options in UTIs has focused on the following phases of the pathogenesis: colonization, adherence of pathogens to uroepithelial cell receptors and invasion. In this review, we discuss vaccines, small compounds, nutraceuticals, immunomodulating agents, probiotics and bacteriophages, highlighting the challenges each of these approaches face. Most of these treatments show interesting but only preliminary results. Lactobacillus-containing products and cranberry products in conjunction with propolis have shown the most robust results to date and appear to be the most promising new alternative to currently used antibiotics. Larger efficacy clinical trials as well as studies on the interplay between non-antibiotic therapies, uropathogens and the host immune system are warranted.

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Section: Small Compoundsmentioning

confidence: 99%

“…Initially, these molecules were used to treat UTIs by preventing urine alkalization ( Griffith et al, 1978 , 1988 ). However, because of the growing evidence of side effects such as mutagenic power, they were progressively phased out ( Munakata et al, 1980 ; Bailie et al, 1986 ; Griffith et al, 1991 ).…”

Section: Small Compoundsmentioning

confidence: 99%

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

et al. 2020

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“…The hydroxamate group and its derivatives were found to be mutagenic as early as three decades ago. [10] Ames tests indicated that some alkyl and aryl hydroxamic acids lead to obvious mutation in strains of the bacterium Salmonella typhimurium . [11] O -Acetyl-benzohydroxamate, a mutagen, was observed to form adducts with DNA and polyguanylic acid in vitro.…”

Section: Mutagenicitymentioning

confidence: 99%

“…Therefore, the amount of the concomitantly released hydroxylamine, which is also a mutagen, is likely insufficient to cause the observed mutagenicity. [10a] …”

Section: Mutagenicitymentioning

confidence: 99%

Why Hydroxamates May Not Be the Best Histone Deacetylase Inhibitors—What Some May Have Forgotten or Would Rather Forget?

2015

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Hydroxamate-based histone deacetylase inhibitors (HDACIs) have been approved as therapeutic agents by the US Food and Drug Administration for use in oncology applications. While the potential utility of such HDACIs in other areas of medicinal chemistry is tremendous, there are significant concerns that “pan-HDAC inhibitors” may be too broadly acting and/or toxic for clinical use beyond oncology. In addition to the isozyme selectivity challenge, the potential mutagenicity of hydroxamate-containing HDAC inhibitors represents a major hindrance in their application to other therapeutic areas. Herein we report on the mutagenicity of known hydroxamates, discuss the mechanisms responsible for their genotoxicity, and review some of the current alternatives to hydroxamates. We conclude that the hydroxamate group, while providing high-potency HDACIs, is not necessarily the best zinc-binding group for HDACI drug discovery.

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“…The formation of such urinary stones was prevented by treatment with urease inhibitors such as hydroxamate (HXA) (1,5,23,26), which has been established to be a potent and specific inhibitor (12). Recently we reported that 2,2'-dimethylpropionylglycino-HXA is a therapeutic agent for such a type of urolithiasis and had a potent inhibitory power (16), high renal clearance (16), and no mutagenicity (17). Based on these findings, Takeuchi et al (24) reported that this compound markedly prevented the formation of bladder stones in rats infected by P. mirabilis.…”

mentioning

confidence: 99%

Stone formation by Ureaplasma urealyticum in human urine and its prevention by urease inhibitors

Takebe¹,

Numata²,

Kobashi³

1984

J Clin Microbiol

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When Ureaplasma urealyticum T-960 was inoculated into normal human urine (108 viable cells per ml of urine), a white precipitate formed, with an increase in pH of the infected urine. This precipitate was identified as a mixture of struvite and whitelockite by analysis of the infrared spectrum. Its formation was completely prevented by the addition of 10 ,LM N-benzoylphosphotriamide, 20 ,uM N-isopentenoylphosphotriamide, or 0.5 mM caprylohydroxamic acid without the alkalinization of the urine, and the Ureaplasma color change units were also decreased markedly by these compounds. The apparent concentrations for 50% inhibition by Nbenzoylphosphotriamide,N-isopentenolyphosphotriamide, and caprylohydroxamic acid against Ureaplasma urease were 7 nM, 2 nM, and 2.2 ,iM, respectively. From these results, it seems that stone formation by U. urealyticum is prevented with these compounds, that prevention being directly attributable to the inhibition of urease activity, which causes the death of the cells.

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Mutagenicity of N-acylglycinohydroxamic acids and related compounds.

Cited by 22 publications

References 13 publications

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

Why Hydroxamates May Not Be the Best Histone Deacetylase Inhibitors—What Some May Have Forgotten or Would Rather Forget?

Stone formation by Ureaplasma urealyticum in human urine and its prevention by urease inhibitors

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