Hygrocins C-G, cytotoxic naphthoquinone ansamycins from gdmAI-disrupted Streptomyces sp. LZ35.
Six hygrocins, polyketides of ansamycin class, were isolated from the gdmAI-disrupted Streptomyces sp. LZ35. The planar structure of hygrocins C-E (1-3) was determined by one-dimensional and two-dimensional NMR spectroscopy and high-resolution mass spectrometry. They are derivatives of hygrocin A but differ in the configuration at C-2 and the orientation of the C-3,4 double bond. Hygrocin F(4) and G(5) were shown to be isomers of hygrocin C (1) and B (6), respectively, due to the different alkyl oxygen participating in the macrolide ester linkage. Hygrocins C, D, and F were found to be toxic to human breast cancer MDA-MB-431 cells (IC50 = 0.5, 3.0, and 3.3 μM, respectively) and prostate cancer PC3 cells (IC50 = 1.9, 5.0, and 4.5 μM, respectively), while hygrocins B, E, and G were inactive.
Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , Jinan 250012, China.
Chunhua
C
Lu
Yaoyao
Y
Li
Jingjing
J
Deng
Shanren
S
Li
Yan
Y
Shen
Haoxin
H
Wang
Yuemao
Y
Shen
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics*
D000970:Antineoplastic Agents; D047029:Lactams, Macrocyclic; D009285:Naphthoquinones