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Sulfanilamide
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Sulfanilamide is a short-acting sulfonamide antibiotic. It is bacteriostatic against most gram-positive and many gram-negative organisms, but many strains of an individual species may be resistant. Sulfanilamide competes with p- aminobenzoic acid (PABA) for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death. Sulfanilamide is used in vaginal cream for the treatment of vulvovaginitis caused by Candida albicans. The active agent sulfanilamide is present in a specially compounded base buffered to the pH (about 4.3) of the normal vagina to encourage the presence of the normally occurring Döderlein’s bacilli in the vagina (1). In Belgium (and probably other countries), it is also available in an ointment for wound treatment.
Antiseptics, antibiotics and chemotherapy
Published in Michael J. O’Dowd, The History of Medications for Women, 2020
During their study of Prontosil, Colebrook and Kenny found that during therapy the patients’ skin had acquired ‘a slightly red or terra-cotta tinge in several of the cases who received large doses of the drug. The urine is always deeply tinged by the dye during the treatment’. The vivid color was caused by the non-active dye component of the Prontosil. It was soon discovered that sulfanilamide was the clinically active portion and that drug went on to replace Prontosil as the treatment of choice in puerperal sepsis. The discovery that sulfanilamide had antibacterial effects led to experimentation with other sulfas and soon sulfathiazole and sulfadiazine were introduced.
The Golden Age of Medicine?
Published in Roger Cooter, John Pickstone, Medicine in the Twentieth Century, 2020
Allan M. Brandt, Martha Gardner
Although Ehrlich’s discovery of a chemotherapy for syphilis was not followed quickly by other anti-microbials, by the 1930s the development of sulfa drugs marked the continued promise of ‘magic bullet’ medicine. In the early 1930s, German biochemist Gerhard Domagk, following Ehrlich’s approach of applying specific dyes, demonstrated that Prontosil, a red dye, cured streptococcal infections in laboratory animals. Soon the medication, whose active component was sulfanilamide, was used with dramatic success to treat streptococcal infections in children as well as puerperal sepsis. A number of other sulfa-based drugs followed to treat a wide range of bacterial infections. While these drugs sometimes did not cure, they did significantly reduce the morbidity and mortality associated with many bacterial infections.
Interaction of drugs with gut microbiota modulators
Published in Drug Metabolism Reviews, 2023
Gut microbiota produce a variety of reductases such as azoreductase and nitroreductase. Gut bacterial azoreductases transform azo compounds under an anaerobic condition in the GI tract. Orally administered prontosil and neoprotosil are transformed to sulfanilamide in the intestine (Gingell et al. 1971; Kim 2015). However, the metabolism of orally administered prontosil and neoprotosil into sulfanilamide is suppressed in vivo by treatment with antibiotics, which shifts gut microbiota composition and quantity (Gingell et al. 1971). Gut microbiota convert sulfasalazine and balsalazide to 5-aminosalicylic acid, which is further metabolized to acetylated mesalazine by gut microbiota (Chan et al. 1983; Klotz 1985). However, antibiotics suppress these modifications such as azo reduction and acetylation and their effectiveness in vivo through the gut microbiota alteration (Chan et al. 1983; Klotz 1985).
Variable sensitivity to diethylene glycol poisoning is related to differences in the uptake transporter for the toxic metabolite diglycolic acid
Published in Clinical Toxicology, 2023
Julie D. Tobin, Courtney N. Jamison, Corie N. Robinson, Kenneth E. McMartin
A pooled analysis of samples from previous studies with rats treated with DEG [12,13] or DGA [8] showed that NaDC-1 mRNA expression was increased in rats with AKI compared with those without AKI. Previous animal studies of DEG or DGA exposure found a wide variability in toxic response, even within groups exposed to the same dose of toxicant. In a single-dose DGA study, only 60% of the animals in the high dose group (300 mg/kg) showed an accumulation of DGA in the kidney and development of severe kidney injury [8]. Similarly in two studies on the repeat-dose toxicity of DEG, slightly more than half of the animals at the highest dose of DEG developed symptoms of poisoning and showed brain and kidney tissue accumulation of DGA [12,13]. A similar variability also occurs in human epidemiological studies of DEG poisoning, although not experimentally examined per se. The sulfanilamide epidemic of 1937 in the US resulted in 260 poisonings, although 353 people ingested the DEG-contaminated preparation [14]. In the Panama epidemic, only 119 cases of AKI were identified from over a thousand people estimated to have been exposed to the DEG-contaminated cough syrup [15]. In a cohort study in the Haiti epidemic, only 32 subjects of the total 49 ingestions showed symptoms of poisoning [16]. This study in animals indicates that the ability of tissues to take up and retain DGA may be an important factor in the variability of toxic effects. It is possible that similar variability in sensitivity to toxicity in humans may also relate to differences in the ability of tissues to take up and retain DGA.
The importance of sulfur-containing motifs in drug design and discovery
Published in Expert Opinion on Drug Discovery, 2022
Muhamad Mustafa, Jean-Yves Winum
In comparison with oxygen, sulfur has a larger atomic size, more diffuse electronic orbitals, and appreciably lower electronegativity. Consequently, special interesting characteristics and properties of sulfur-containing functions in terms of bioisosteric replacement, pharmacophoric and pharmacological properties, and metabolic stability have been exploited in drug design to modulate the potency of a small-molecule therapeutic against its biological target. Since the first ‘sulfa drugs’ used as antibacterial compounds and exemplified by Prontosyl discovery in 1932 and its metabolite the sulfanilamide, the versatility of sulfur compounds as drugs has been demonstrated in all classes of therapeutic agents ranging from antivirals, antibacterial, antitumoral, antifungals, antiparasites, anti-glaucoma, etc.