Synthesis and evaluation of macrocyclic diarylether heptanoid natural products and their analogs

被引：29

作者：

Bryant, Vashti C. ^{[1
,2
]}

Kumar, G. D. Kishore ^{[2
]}

Nyong, Abijah M. ^{[1
]}

Natarajan, Amarnath ^{[1
,2
]}

机构：

[1] Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA

[2] Univ Texas Med Branch, Chem Biol Program, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 01期

关键词：

Macrocyclic diarylether heptanoid; Pancreatic cancer; NF-kappa B; Grubbs/Ullmann; Total synthesis; FACTOR-KAPPA-B; DIARYLHEPTANOIDS; CANCER;

D O I：

10.1016/j.bmcl.2011.11.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-kappa B. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growth inhibition and apoptosis. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：245 / 248

页数：4

共 20 条

[1] Inflammation and the development of pancreatic cancer [J].

Farrow, B ;

Evers, BM .

SURGICAL ONCOLOGY-OXFORD, 2002, 10 (04) :153-169

[2]

Fujioka S, 2003, CLIN CANCER RES, V9, P346

[3] Cysteine 38 in p65/NF-κB plays a crucial role in DNA binding inhibition by sesquiterpene lactones [J].

García-Piñeres, AJ ;

Castro, V ;

Mora, G ;

Schmidt, TJ ;

Strunck, E ;

Pahl, HL ;

Merfort, I .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (43) :39713-39720

[4] First total synthesis of acerogenin C and aceroside IV [J].

Gonzalez, GI ;

Zhu, JP .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (22) :7544-7545

[5] Natural products in drug discovery [J].

Harvey, Alan L. .

DRUG DISCOVERY TODAY, 2008, 13 (19-20) :894-901

[6] A versatile synthesis of cyclic diphenyl ether-type diarylheptanoids:: Acerogenins, (±)-galeon, and (±)-pterocarine [J].

Jeong, Byeong-Seon ;

Wang, Qian ;

Son, Jong-Keun ;

Jahng, Yurngdong .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2007, 2007 (08) :1338-1344

[7] Diarylheptanoids from Alnus hirsuta inhibit the NF-kB activation and NO and TNF-α production [J].

Jin, WenYi ;

Cai, Xing Fu ;

Na, MinKyun ;

Lee, Jung Joon ;

Bae, KiHwan .

BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2007, 30 (04) :810-813

[8]

Keseru GM, 1998, EUR J ORG CHEM, V1998, P521, DOI 10.1002/(SICI)1099-0690(199803)1998:3<521::AID-EJOC521>3.0.CO

[9]

2-I

[10] Total synthesis of ovalifoliolatin B, acerogenins A and C [J].

Kumar, G. D. Kishore ;

Natarajan, Amarnath .

TETRAHEDRON LETTERS, 2008, 49 (13) :2103-2105

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