Soft drugs. 1. Labile quaternary ammonium salts as soft antimicrobials

Bodor, Nicholas; Kaminski, James J.; Selk, Sally H.

doi:10.1021/jm00179a001

Cited by 153 publications

(87 citation statements)

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“…These biologically active compounds are readily degraded into non-toxic and biologically inactive products in vivo, as well as in the environment. The concept of soft antibacterial agents was proposed over 20 years ago (20), and a number have been synthesised and tested both in vitro and in vivo. Thorstein et al (17) synthesised a series of analogues of benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC), which showed satisfactory antibacterial properties and were characterised by good chemical stability and ready non-enzymatic and enzymatic degradation to original, non-toxic building blocks.…”

Section: Cationic Surfactantsmentioning

confidence: 99%

Surfactants in the Environment

Ivanković

Hrenović

2010

Archives of Industrial Hygiene and Toxicology

334

190

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Surfactants in the EnvironmentSurfactants are a diverse group of chemicals that are best known for their wide use in detergents and other cleaning products. After use, residual surfactants are discharged into sewage systems or directly into surface waters, and most of them end up dispersed in different environmental compartments such as soil, water or sediment. The toxic effects of surfactants on various aquatic organisms are well known. In general, surfactants are present in the environment at levels below toxicity and in Croatia below the national limit. Most surfactants are readily biodegradable and their amount is greatly reduced with secondary treatment in wastewater treatment plants. The highest concern is the release of untreated wastewater or wastewater that has undergone primary treatment alone. The discharge of wastewater polluted with massive quantities of surfactants could have serious effects on the ecosystem. Future studies of surfactant toxicities and biodegradation are necessary to withdraw highly toxic and non-biodegradable compounds from commercial use and replace them with more environmentally friendly ones.

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Section: Cationic Surfactantsmentioning

confidence: 99%

Surfactants in the Environment

Ivanković

Hrenović

2010

Archives of Industrial Hygiene and Toxicology

334

190

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“…The hydrolysis step should preferably lead not only to a nonactive compound but also to degradation products that are significantly less toxic than the original substance. Compounds based on this type of concept were originally developed by Bodor et al (2) and were introduced as ''soft'' drugs. Soft drugs are defined as biologically active, therapeutically useful compounds characterized by a controllable degradation to nontoxic moieties after they achieve their therapeutic effect.…”

mentioning

confidence: 99%

“…Soft drugs are defined as biologically active, therapeutically useful compounds characterized by a controllable degradation to nontoxic moieties after they achieve their therapeutic effect. This concept can be applied to limit the toxicities of antimicrobial agents, and the first soft drug to be introduced was actually an antimicrobial agent (2).…”

mentioning

confidence: 99%

Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable

Ahlström

Chelminska-Bertilsson

Thompson

et al. 1995

Antimicrob Agents Chemother

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A new category of amphiphilic hydrolyzable quaternary ammonium compounds with rapid and high levels of antimicrobial activity was studied. The compounds, alkanoylcholines with hydrocarbon chains of 10 to 14 carbon atoms, are hydrolyzed by butyrylcholine esterase, which is present in human serum and mucosal membranes. The hydrolysis products are common components of human metabolism. Alkanoylcholines were tested and found to be active against gram-negative and gram-positive bacteria as well as yeasts. The microbicidal activities of the alkanoylcholines were comparable to the activities of the stable quaternary ammonium compounds of corresponding chain length and increased with an increasing number of carbon atoms. The compounds were also found to be hydrolyzed by enzymes present in certain microorganisms. The degradation was achieved after reaching the microbicidal effect.

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“…One of the most recent approaches to produce an effective but safe drug is the so-called retrometabolic drug design. Retrometabolically designed drug candidates have already been under investigation in widely different pharmacological fields intended to use as antiglaucoma agents (Bodor, 1989), antimicrobials (Bodor et al, 1980a), antitumor compounds (Bodor and Kaminski, 1980), or as short-acting anticholinergics (Bodor et al, 1980b). As the site of intended action and the site of administration coincide in inhalation therapy, the potential for the application of the retrometabolic approach in the treatment of asthma with ICS is especially promising.…”

Section: Discussionmentioning

confidence: 99%

Potency and Specificity of the Pharmacological Action of a New, Antiasthmatic, Topically Administered Soft Steroid, Etiprednol Dicloacetate (BNP-166)

Kurucz¹,

Tóth²,

Németh³

et al. 2003

J Pharmacol Exp Ther

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In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17␣-dichloroacetoxy-11␤-hydroxyandrosta-1,4-diene-3-one-17␤-carboxylate), a new soft steroid, intended to use for the treatment of asthma, were investigated in an animal model of allergen sensitized and challenged Brown Norway rats using local treatment. The examinations involved the determination of the effect of the compound on the extent of allergen induced broncho-alveolar fluid and lung tissue eosinophilia, goblet cell hyperplasia and mucus production, perivascular edema formation, and airways hyperresponsiveness. The activity of etiprednol dicloacetate was compared with that of budesonide. Using in vitro methods, the soft character of etiprednol dicloacetate was investigated together with its capability to dissociate transrepressing and transactivating properties. We found that combining all the examined parameters etiprednol dicloacetate was at least equipotent with budesonide in the animal model, but in several investigated variables it surpassed the activity of budesonide. The effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of the serum, present in the assay, it was also strongly affected by the incubation time and decreased significantly when it was preincubated with human plasma. These features are characteristics of a soft drug that is quickly inactivated in the systemic circulation. In addition, it was revealed that while the transrepressing potential of etiprednol dicloacetate remained high, its transactivating activity was greatly reduced. These data indicate that the strong local effect of the compound will very likely be accompanied with a significantly reduced systemic activity predicting favorable selectivity in the pharmacological action of etiprednol dicloacetate.

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Soft drugs. 1. Labile quaternary ammonium salts as soft antimicrobials

Cited by 153 publications

References 0 publications

Surfactants in the Environment

Surfactants in the Environment

Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable

Potency and Specificity of the Pharmacological Action of a New, Antiasthmatic, Topically Administered Soft Steroid, Etiprednol Dicloacetate (BNP-166)

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