Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94

被引：13

作者：

Abdelhakim, Islam A. ^{[1
,2
,3
,4
]}

Bin Mahmud, Fauze ^{[1
,5
,6
]}

Motoyama, Takayuki ^{[1
]}

Futamura, Yushi ^{[1
]}

Takahashi, Shunji ^{[4
]}

Osada, Hiroyuki ^{[1
]}

机构：

[1] RIKEN CSRS, Chem Biol Res Grp, Wako, Saitama 3510198, Japan

[2] Saitama Univ, Grad Sch Sci & Engn, Sakura, Saitama 3388570, Japan

[3] Assiut Univ, Fac Pharm, Assiut 71515, Egypt

[4] RIKEN CSRS, Nat Prod Biosynth Res Unit, Wako, Saitama 3510198, Japan

[5] Univ Sains Malaysia, Inst Res Mol Med, George Town 11800, Penang, Malaysia

[6] Univ Malaysia Sabah, Fac Sci & Nat Resources, Kota Kinabalu 88400, Sabah, Malaysia

来源：

JOURNAL OF NATURAL PRODUCTS | 2022年 / 85卷 / 01期

关键词：

BIOSYNTHETIC GENE-CLUSTER; METABOLITES; IDENTIFICATION; EXPRESSION; LIBRARY;

D O I：

10.1021/acs.jnatprod.1c00677

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

A recently discovered secondary metabolism regulator, NPD938, was used to alter the secondary metabolite profile in Fusarium sp. RK97-94. Three lucilactaene analogues were detected via UPLC-ESI-MS analysis in NPD938-treated culture. The three metabolites were successfully purified and identified as dihydroNG391 (1), dihydrolucilactaene (2), and 13 alpha-hydroxylucilactaene (3) via extensive spectroscopic analyses. DihydroNG391 (1) exhibited weak in vitro antimalarial activity (IC50 = 62 mu M). In contrast, dihydrolucilactaene (2) and 13 alpha-hydroxylucilactaene (3) showed very potent antimalarial activity (IC50 = 0.0015 and 0.68 mu M, respectively). These findings provide insight into the structure-activity relationship of lucilactaene and its analogues as antimalarial lead compounds.

引用

页码：63 / 69

页数：7

共 34 条

[1]

Bashyal BP, 2007, NAT PROD COMMUN, V2, P547

[2] Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans [J].

Bergmann, Sebastian ;

Schuemann, Julia ;

Scherlach, Kirstin ;

Lange, Corinna ;

Brakhage, Axel A. ;

Hertweck, Christian .

NATURE CHEMICAL BIOLOGY, 2007, 3 (04) :213-217

[3] Metabolites from the Induced Expression of Cryptic Single Operons Found in the Genome of Burkholderia pseudomallei [J].

Biggins, John B. ;

Liu, Xiaofei ;

Feng, Zhiyang ;

Brady, Sean F. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (06) :1638-1641

[4]

Bode HB, 2002, CHEMBIOCHEM, V3, P619, DOI 10.1002/1439-7633(20020703)3:7<619::AID-CBIC619>3.0.CO

[5]

2-9

[6]

Bok J. W., 2006, CHEM BIOL, V74, P6761

[7] GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence [J].

Bok, Jin Woo ;

Chung, DaWoon ;

Balajee, S. Arunmozhi ;

Marr, Kieren A. ;

Andes, David ;

Nielsen, Kristian Fog ;

Frisvad, Jens C. ;

Kirby, Katharine A. ;

Keller, Nancy P. .

INFECTION AND IMMUNITY, 2006, 74 (12) :6761-6768

[8] Regulation of fungal secondary metabolism [J].

Brakhage, Axel A. .

NATURE REVIEWS MICROBIOLOGY, 2013, 11 (01) :21-32

[9] Chemical Perturbation of Secondary Metabolism Demonstrates Important Links to Primary Metabolism [J].

Craney, Arryn ;

Ozimok, Cory ;

Pimentel-Elardo, Sheila Marie ;

Capretta, Alfredo ;

Nodwell, Justin R. .

CHEMISTRY & BIOLOGY, 2012, 19 (08) :1020-1027

[10] The diastereoselective asymmetric total synthesis of NG-391, a neuronal cell-protecting molecule [J].

Hayashi, Y ;

Yamaguchi, J ;

Shoji, M .

TETRAHEDRON, 2002, 58 (49) :9839-9846

← 1 2 3 4 →