China
Africa
Explore chapters and articles related to this topic
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.
Cutaneous Photosensitization
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
Phenothiazine derivatives photosensitize cleavage of DNA and form covalent photoadducts with DNA and nucleotide bases.6 Phototoxicity of the tetracyclines have been demonstrated by in vitro cell culture methods using selected tetracyclines plus UVA radiation to inhibit polymorphonuclear leukocyte migration.7 Phototoxicity induced by the nonsteroidal anti-inflammatory drug (NSAID), benoxaprofen, is attributed to membrane photosensitization. Specifically, mast cell degranulation due to interaction of the mast cell membrane with benoxaprofen and light, is responsible for the urticarial lesions seen in clinical cases. Piroxicam, another NSAID, is responsible for both photoallergy and phototoxicity. Testing results suggest that piroxicam photosensitivity may involve the formation of a metabolite that is preferentially formed or accumulated in the skin.8 Likewise, sulfanilamide appears to induce both photoallergic and phototoxic reactions in skin by free radical mechanisms.9 The photoinduced binding of sulfanilamide to protein and DNA also has been demonstrated.10
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.
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.
Antibacterial carbonic anhydrase inhibitors: an update on the recent literature
Published in Expert Opinion on Therapeutic Patents, 2020
Claudiu T. Supuran, Clemente Capasso
Sulfonamides, together with the inorganic anions, are the most investigated CA inhibitors (CAIs) [18,29,47,48]. Domagk discovered the antimicrobial sulfonamides in 1935 [49], and they were the first antimicrobial drugs to be widely used in clinical settings. The first sulfonamide showing effective antibacterial activity was Prontosil, a sulfanilamide prodrug, the last compound being isosteric/isostructural with p-aminobenzoic acid (PABA), the substrate of dihydropteroate synthase (DHPS) [50]. In the following years after sulfanilamide was shown to be an effective antibacterial agent, a range of analogs constituting the so-called sulfa drug class of antibacterials entered into clinical use, and many of these compounds are still widely used, despite significant drug resistance problems. DHPS, as mentioned above, is the target of the sulfa drugs. Several DHPS mutations are responsible for the sulfonamide resistance [5]. However, the presence of primary sulfonamide moieties in sulfanilamide also endows it with CA inhibitory properties [27,29]. Thus, a range of compounds incorporating SO2NH2 groups were investigated as CAIs against bacterial CAs (and of course also against CAs present in other organisms) [27,29].