每周分子 | Molecule of the Week

Original ACS美国化学会 ACS美国化学会 2022-07-01

每周分子: ‍两性霉素B‍

Molecule of the Week: Amphotericin B

两性霉素B是由细菌链霉菌(Streptomyces nodosus)产生的抗真菌抗生素。 1955年，它被Squibb医学研究所的研究人员从委内瑞拉奥里诺科河附近收集的土壤中分离出来，该研究所现在是Bristol-Meyers Squibb (New Brunswick, NJ)的一部分。

美国罗格斯大学(位于新布朗斯维克)的Carl P. Schaffner和共同作者在1965年阐明了两性霉素B的完整结构和绝对构型。该分子的全合成由位于费城的美国宾夕法尼亚大学教授 K. C. Nicolaou完成，直到20世纪80年代，该化合物才是针对全身性真菌疾病的唯一有效药物。

现在，两性霉素B可能具有新的重要医学用途。美国伊利诺伊大学厄巴纳 - 香槟分校的Martin D. Burke及其同事表示，当对从囊性纤维化患者的肺气道内层取出的培养上皮细胞给药时，该药物产生了新的离子通道来代替那些被囊性突变阻断的纤维化跨膜传导调节因子(CFTR)蛋白。该方法增加了pH并降低了衬里表面上分泌的液体的粘度，从而改善了碳酸氢根离子的流动性。

作者与美国爱荷华大学(位于爱荷华市)的囊性纤维化研究员Michael J. Welsh一起，用两性霉素B治疗缺乏CFTR蛋白的猪。再次，气道表面液体的pH增加，表明两性霉素B可以在CFTR蛋白突变或甚至不存在时，对囊性纤维化有效。临床试验将随之而来。

两性霉素B信息速览

CAS登记号	1397-89-3
分子式	C₄₇H₇₃NO₁₇
摩尔质量	924.09 g/mol
外观	黄色菱柱或针状
熔点	>170 ºC (dec.)
水溶性	750 mg/L

两性霉素B危害信息

GHS分类*：物质或混合物无害

【关于每周分子】

自2001年以来，“每周分子”已成为广受欢迎的栏目。多数分子由读者推荐。每个结构都经由科学家审查，并以3-D和平面图像的形式显示，同时附有该分子简介。可以通过美国化学文摘社（CAS）提供的SciFinder中的CAS REGISTRY获取“每周分子”的更多信息。CAS REGISTRY中的每条物质信息都展示了物质的CAS登记号、索引名、通用名、商品名、书目信息等其他更多信息。发送邮件至motw@acs.org推荐您感兴趣的分子吧。

Amphotericin B is an antifungal antibiotic produced by the bacterium Streptomyces nodosus. In 1955, it was isolated from soil collected near the Orinoco River of Venezuela by researchers at the Squibb Institute for Medical Research, now part of Bristol-Meyers Squibb (New Brunswick, NJ).

Carl P. Schaffner at Rutgers University (New Brunswick) and coauthors elucidated the complete structure and absolute configuration of amphotericin B in 1965. The molecule’s total synthesis was completed by K. C. Nicolaou, then at the University of Pennsylvania (Philadelphia) and co-workers in 1987. Until the 1980s, the compound was the only effective medication against systemic fungal diseases.

Now amphotericin B could have a new, important medical use. Martin D. Burke and colleagues at the University of Illinois at Urbana–Champaign showed that, when administered to cultured epithelial cells taken from the lung airway linings of cystic fibrosis patients, the drug created new ion channels to replace those blocked by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This procedure increased the pH and lowered the viscosity of the liquid secreted on the lining surfaces, resulting in improved bicarbonate ion flow.

The authors, together with cystic fibrosis researcher Michael J. Welsh at the University of Iowa (Iowa City), then treated pigs that lacked the CFTR protein with amphotericin B. Again, the pH of the airway surface liquid increased, showing that amphotericin B could be effective against cystic fibrosis when the CFTR protein is mutated or even absent. Clinical trials will follow.

Amphotericin B fast facts

CAS Reg. No.	1397-89-3
Empirical formula	C₄₇H₇₃NO₁₇
Molar mass	924.09 g/mol
Appearance	Deep yellow prisms or needles
Melting point	>170 ºC (dec.)
Water solubility	750 mg/L

Amphotericin B hazard information

GHS classification*: not a hazardous substance or mixture

* Globally Harmonized System of Classification and Labeling of Chemicals.

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