title: A newly identified derivative of amphotericin B: isolation, structure determination and primary evaluation of the activity and toxicity.
abstract: A new derivative of amphotericin B named amphotericin B(5) has been obtained under the following condition: amphotericin B powder was first dissolved in N,N-dimethylformamide at room temperature to obtain a solution of concentration of 2.0 mg ml(-1). Then, the solution was kept at 60 °C in an electric-heated thermostatic water bath for 48-60 h for the purpose of accelerating the degradation. Amphotericin B(5) was isolated by preparative HPLC. Its structure has been identified by means of UV, NMR and LCMS-IT-TOF as (1R, 3S, 5R, 6R, 9R, 11R, 15S, 16R, 17R, 18S, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R, 35S, 36R, 37S)-33-[3-form-amide-3,6-dideoxy-β--mannopy-ran-osyl)oxy]-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-di-oxabicyclo [33.3.1] nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid named according to the International Union of Pure and Applied Chemistry. The activity of amphotericin B(5) was tested against Saccharomyces cerevisiae based on microbiological potency using cylinder-plate method, and the toxicities of amphotericin B and amphotericin B(5) were determined simultaneously in zebrafish embryo. The results showed that the toxicity of amphotericin B(5), as revealed by its LD(50) value, was lower than amphotericin B.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Jing-Pu
authors.initials: JP
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.forename: Chang-Qin
authors.initials: CQ
authors.lastname: Hu
mesh_terms: D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D016019:Survival Analysis; D015027:Zebrafish
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B