Fotso Serge, Zabriskie T Mark, Proteau Philip J, Flatt Patricia M, Santosa Dwi Andreas, Mahmud Taifo
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331-3507, USA
J Nat Prod. 2009 Apr;72(4):690-5. doi: 10.1021/np800827w.
In our screening of Indonesian microorganisms for novel bioactive natural products we have isolated seven new compounds, designated as limazepines A, B1 and B2 (isolated as an isomeric mixture), C, D, E, and F, from the culture broth of Micrococcus sp. strain ICBB 8177. In addition, the known natural products prothracarcin and 7-O-succinylmacrolactin A, as well as two previously reported synthetic compounds, 2-amino-3-hydroxy-4-methoxybenzoic acid methyl ester and 4-ethylpyrrole-2-carboxaldehyde, were obtained from the extract. Chemical structures were determined by spectroscopic methods and by comparison with the NMR data of structurally related compounds. The limazepines belong to the growing group of the pyrrolo[1,4]benzodiazepine antitumor antibiotics isolated from various soil bacteria. Limazepines B1/B2 mixture, C, and E were active against the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli. Limazepine D was also active against S. aureus, but was not active against E. coli. Interestingly, only the limazepines B1/B2 mixture and D were active against Pseudomonas aeruginosa.
在我们对印度尼西亚微生物进行新型生物活性天然产物筛选的过程中,我们从微球菌属菌株ICBB 8177的培养液中分离出了7种新化合物,分别命名为利马泽平A、B1和B2(以异构体混合物形式分离)、C、D、E和F。此外,还从提取物中获得了已知的天然产物原蒽环素和7 - O - 琥珀酰大环内酯A,以及两种先前报道的合成化合物,2 - 氨基 - 3 - 羟基 - 4 - 甲氧基苯甲酸甲酯和4 - 乙基吡咯 - 2 - 甲醛。通过光谱方法并与结构相关化合物的核磁共振数据进行比较确定了化学结构。利马泽平属于从各种土壤细菌中分离出的不断增加的吡咯并[1,4]苯并二氮杂䓬类抗肿瘤抗生素。利马泽平B1/B2混合物、C和E对革兰氏阳性菌金黄色葡萄球菌和革兰氏阴性菌大肠杆菌有活性。利马泽平D对金黄色葡萄球菌也有活性,但对大肠杆菌无活性。有趣的是,只有利马泽平B1/B2混合物和D对铜绿假单胞菌有活性。