Cytotoxic and antihaptotactic beauvericin analogues from precursor-directed biosynthesis with the insect pathogen Beauveria bassiana ATCC 7159

被引：63

作者：

Xu, Yuquan ^{[1
]}

Zhan, Jixun ^{[1
]}

Wijeratne, E. M. Kithsiri ^{[1
]}

Burns, Anna M. ^{[1
]}

Gunatilaka, A. A. Leslie ^{[1
]}

Molnar, Istvan ^{[1
]}

机构：

[1] Univ Arizona, Coll Agr & Life Sci, Off Arid Studies, SW Ctr Nat Prod Res & Commercializat, Tucson, AZ 85706 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2007年 / 70卷 / 09期

关键词：

D O I：

10.1021/np070262f

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Precursor-directed biosynthesis was used to produce analogues of the cyclic depsipeptide mycotoxin beauvericin (1) using the filamentous fungus Beauveria bassiana ATCC 7159. Feeding 30 analogues Of D-2-hydroxyisovalerate and L-phenylalanine, the natural 2-hydroxycarboxylic acid and amino acid precursors of beauvericin, led to the biosynthesis of novel beauvericins. Six of these were isolated and characterized, and their cytotoxicity and directional cell migration (haptotaxis) inhibitory activity against the metastatic prostate cancer cell line PC-3M were evaluated. Replacement of one, two, or all three of the D-2-hydroxyisovaterate constituents in beauvericin (1) with 2-hydroxybutyrate moieties (beauvericins G(1-3), compounds 2-4) caused a parallel decline of cell migration inhibitory activity and cytotoxicity, suggesting a requirement for a branched side chain for both of these biological activities at the corresponding positions of beauvericins. Replacement of one; two, or all three N-methyl-L-phenylalanine residues of beauvericin with N-methyl-L-3-fluorophenylalanine moieties (beauvericins H1-3, compounds 5-7) increased cytotoxicity without affecting antihaptotactic activity.

引用

页码：1467 / 1471

页数：5