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来自海洋沉积物相关链霉菌属菌株KNIM 9048的金霉素抗肿瘤抗生素复合物。

The Antitumor Antibiotics Complex of Aureolic Acids from the Marine Sediment-associated Strain of Streptomyces sp. KNIM 9048.

作者信息

Kalinovskaya Nataliya L, Romanenko Lyudmila A, Kalinovsky Anatoly I, Ermakova Svetlana P, Dmitrenok Pavel S, Afiyatulov Shamil Sh

出版信息

Nat Prod Commun. 2017 Apr;12(4):571-577.

Abstract

A new antibiotic complex of six aureolic acids was isolated from the marine sediment-associated strain Streptomyces sp. KMM 9048. Four of the compounds (3-6) were found to be similar but not identical to the known chromomycins A₂, A₃, demethyl chromomycin A₃ and A₄. The two remaining.compounds; A₂₋₁ (1) and A₃₋₁ (2), were established as novel chromomycin analogs, which did not contain sugar B. Spectroscopic methods including ID and 2D NMR, and HRMS and MS/MS were applied for structure elucidation. Compounds 1-5 showed strong antimicrobial activity against Gram-positive indicatory bacteria Enterococcusfaecium, Staphylococcus aureus, S. epidernzidis, and Bacillus subtilis. Antitumor assay indicated that all tested compounds, in different manners, inhibited colony formation of RPMI-7951 and SK-Mel-28 cancer cells. This is the first study reporting the inhibitory effects of chromomycin analogs 1-5 on the colony formation of the investigated cancer cell lines. Compound 3, in a concentration of 5 nM, inhibited colony formation of RPMI-7951 and SK-Mel-28 cells by 82 % and 72 %, respectively. Our finding indicated that, of the compounds tested, 3 and 4 are promising anticancer and antimicrobial agents.

摘要

从海洋沉积物相关菌株链霉菌属KMM 9048中分离出一种由六种金霉素酸组成的新型抗生素复合物。发现其中四种化合物(3 - 6)与已知的色霉素A₂、A₃、去甲基色霉素A₃和A₄相似但不完全相同。其余两种化合物,A₂₋₁(1)和A₃₋₁(2),被确定为新型色霉素类似物,它们不含糖B。采用包括一维和二维核磁共振、高分辨质谱和串联质谱在内的光谱方法进行结构解析。化合物1 - 5对革兰氏阳性指示菌粪肠球菌、金黄色葡萄球菌、表皮葡萄球菌和枯草芽孢杆菌表现出较强的抗菌活性。抗肿瘤试验表明,所有测试化合物均以不同方式抑制RPMI - 7951和SK - Mel - 28癌细胞的集落形成。这是首次报道色霉素类似物1 - 5对所研究癌细胞系集落形成的抑制作用的研究。化合物3在浓度为5 nM时,分别抑制RPMI - 7951和SK - Mel - 28细胞集落形成82%和72%。我们的研究结果表明,在所测试的化合物中,3和4是有前景的抗癌和抗菌剂。

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