Safety of Benzoic anhydride. In 2019 J AM CHEM SOC published article about RIBOSOMAL-RNA METHYLASES; ANTIBIOTICS; TARGET; SITE; CONFIGURATION; MECHANISMS; MUTATIONS; HEARING; ENZYMES; BINDING in [Matsushita, Takahiko; Sati, Girish C.; Kondasinghe, Nuwan; Pirrone, Michael G.; Kato, Takayuki; Waduge, Prabuddha; Chow, Christine S.; Crich, David] Wayne State Univ, Dept Chem, 5101 Cass Ave, Detroit, MI 48202 USA; [Kumar, Harshitha Santhosh; Sanchon, Adrian Cortes; Shcherbakov, Dimitri; Juhas, Mario; Hobbie, Sven N.; Bottger, Erik C.] Univ Zurich, Inst Med Mikrobiol, 28 Gloriastr, CH-8006 Zurich, Switzerland; [Dobosz-Bartoszek, Malgorzata; Polikanov, Yury S.] Univ Illinois, Dept Biol Sci, 900 South Ashland Ave, Chicago, IL 60607 USA; [Schrepfer, Thomas; Schacht, Jochen] Univ Michigan, Kresge Hearing Res Inst, Dept Otolaryngol, 1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA; [Polikanov, Yury S.] Univ Illinois, Dept Med Chem & Pharmacognosy, 900 South Ashland Ave, Chicago, IL 60607 USA; [Vasella, Andrea] Swiss Fed Inst Technol, Lab Organ Chem, Vladimir Prelog Weg 1-5-10, CH-8093 Zurich, Switzerland in 2019, Cited 56. The Name is Benzoic anhydride. Through research, I have a further understanding and discovery of 93-97-0.
Infectious diseases due to multidrug-resistant pathogens, particularly carbapenem-resistant Enterobacteriaceae (CREs), present a major and growing threat to human health and society, providing an urgent need for the development of improved potent antibiotics for their treatment. We describe the design and development of a new class of aminoglycoside antibiotics culminating in the discovery of propylamycin. Propylamycin is a 4′-deoxy-4′-alkyl paromomycin whose alkyl substituent conveys excellent activity against a broad spectrum of ESKAPE pathogens and other Gram-negative infections, including CREs, in the presence of numerous common resistance determinants, be they aminoglycoside modifying enzymes or rRNA methyl transferases. Importantly, propylamycin is demonstrated not to be susceptible to the action of the ArmA resistance determinant whose presence severely compromises the action of plazomicin and all other 4,6-disubstituted 2-deoxystreptamine aminoglycosides. The lack of susceptibility to ArmA, which is frequently encoded on the same plasmid as carbapenemase genes, ensures that propylamycin will not suffer from problems of cross-resistance when used in combination with carbapenems. Cell-free translation assays, quantitative ribosome footprinting, and X-ray crystallography support a model in which propylamycin functions by interference with bacterial protein synthesis. Cell-free translation assays with humanized bacterial ribosomes were used to optimize the selectivity of propylamycin, resulting in reduced ototoxicity in guinea pigs. In mouse thigh and septicemia models of Escherichia coli, propylamycin shows excellent efficacy, which is better than paromomycin. Overall, a simple novel deoxy alkyl modification of a readily available aminoglycoside antibiotic increases the inherent antibacterial activity, effectively combats multiple mechanisms of aminoglycoside resistance, and minimizes one of the major side effects of aminoglycoside therapy.
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Reference:
Isothiazole – Wikipedia,
,Isothiazole – ScienceDirect.com