Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311.

Antileishmanial macrolides from ant-associated Streptomyces sp. ISID311.
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DOI:
10.1016/j.bmc.2021.116016
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发表时间:
2021-02-15
影响因子:
3.5
通讯作者:
Pupo MT
Pupo MT
中科院分区:
医学3区
文献类型:
--
作者:
Ortega HE;Lourenzon VB;Chevrette MG;Ferreira LLG;Alvarenga RFR;Melo WGP;Venâncio T;Currie CR;Andricopulo AD;Bugni TS;Pupo MT

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从一种与Cyphomyrmex真菌生长蚂蚁共生的细菌Streptomyces sp.ISID311中分离得到3个抗真菌大环内酯类化合物cyphomycin(1)、canifercin C(2)和GT-35(3)。这些化合物的平面结构通过一维和二维NMR数据和MS分析确定。采用Kishís通用NMR数据库法、NOE/ROE分析和偶合常数分析,结合相关化合物的NMR数据,确定了1-3的相对构型。对Cyphomycin生物合成基因簇的详细生物信息学分析证实了立体化学归属。化合物1-3对不同菌株的Escovopsis sp.均表现出较强的拮抗作用,专属于真菌生长蚂蚁系统的病原真菌。化合物1-3对杜氏利什曼原虫胞内无鞭毛体也表现出较强的抗原虫活性,IC 50值分别为2.32、0.091和0.073 μM,选择性指数较高。
Three antifungal macrolides cyphomycin (1), caniferolide C (2) and GT-35 (3) were isolated from Streptomyces sp. ISID311, a bacterial symbiont associated with Cyphomyrmex fungus-growing ants. The planar structures of these compounds were established by 1 and 2D NMR data and MS analysis. The relative configurations of 1–3 were established using Kishís universal NMR database method, NOE/ROE analysis and coupling constants analysis assisted by comparisons with NMR data of related compounds. Detailed bioinformatic analysis of cyphomycin biosynthetic gene cluster confirmed the stereochemical assignments. Compounds 1–3 displayed high antagonism against different strains of Escovopsis sp., pathogen fungi specialized to the fungus-growing ant system. Compounds 1–3 also exhibited potent antiprotozoal activity against intracellular amastigotes of the human parasite Leishmania donovani with IC50 values of 2.32, 0.091 and 0.073 μM, respectively, with high selectivity indexes.
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