Synthesis and antimalarial activity of new haemanthamine-type derivatives

被引：32

作者：

Cedron, Juan C. ^{[1
,2
]}

Gutierrez, David ^{[3
]}

Flores, Ninoska ^{[3
]}

Ravelo, Angel G. ^{[1
]}

Estevez-Braun, Ana ^{[1
]}

机构：

[1] Univ La Laguna, Dept Quim Organ, Inst Univ BioOrgan Antonio Gonzalez, Tenerife, Spain

[2] Pontificia Univ Catolica Peru, Secc Quim, Lima 32, Peru

[3] Univ Mayor San Andres, Fac Ciencias Farmaceut & Bioquim, Inst Invest Farmaco Bioquim, La Paz, Bolivia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 18期

关键词：

Haemanthamine; Antiplasmodial activity; Amaryllidaceae alkaloids; NATURAL-PRODUCTS; ALKALOIDS; AMARYLLIDACEAE;

D O I：

10.1016/j.bmc.2012.07.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Thirty one derivatives were prepared from the natural alkaloids haemanthamine (1), haemanthidine (2) and 11-hydroxyvittatine (3). They were evaluated for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum and some structure-activity relationships were outlined. For haemanthamine derivatives having a methoxy group at C-3, the presence of a free hydroxyl group at C-11 is important for the activity. The double bond at C-1-C-2 plays also an important role to achieve good inhibitory activity. Compound 35 with two nicotinate groups at C-3 and at C-11 was the most active compound with a IC50 = 0.8 +/- 0.06 mu M. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5464 / 5472

页数：9

共 25 条

[1]

Cabezas F, 2003, CHEM PHARM BULL, V51, P315

[2] Alkaloids from South African Amaryllidaceae -: Part 7 -: Bioactive alkaloids from Brunsvigia radulosa [J].

Campbell, WE ;

Nair, JJ ;

Gammon, DW ;

Codina, C ;

Bastida, J ;

Viladomat, F ;

Smith, PJ ;

Albrecht, CF .

PHYTOCHEMISTRY, 2000, 53 (05) :587-591

[3] Aplidiopsamine A, an Antiplasmodial Alkaloid from the Temperate Australian Ascidian, Aplidiopsis confluata [J].

Carroll, Anthony R. ;

Duffy, Sandra ;

Avery, Vicky M. .

JOURNAL OF ORGANIC CHEMISTRY, 2010, 75 (23) :8291-8294

[4] Synthesis and antiplasmodial activity of lycorine derivatives [J].

Cedron, Juan C. ;

Gutierrez, David ;

Flores, Ninoska ;

Ravelo, Angel G. ;

Estevez-Braun, Ana .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (13) :4694-4701

[5]

Cedrón JC, 2010, ALKALOIDS-CHEM BIOL, V68, P1, DOI 10.1016/S1099-4831(10)06801-X

[6] Pancratium canariense as an Important Source of Amaryllidaceae Alkaloids [J].

Cedron, Juan C. ;

Oberti, Juan C. ;

Estevez-Braun, Ana ;

Ravelo, Angel G. ;

Del Arco-Aguilar, Marcelino ;

Lopez, Matias .

JOURNAL OF NATURAL PRODUCTS, 2009, 72 (01) :112-116

[7] Bioactive Montanine Derivatives from Halide-induced Rearrangements of Haemanthamine-type Alkaloids. Absolute Configuration by VCD [J].

Cedron, Juan C. ;

Estevez-Braun, Ana ;

Ravelo, Angel G. ;

Gutierrez, David ;

Flores, Ninoska ;

Bucio, Maria A. ;

Perez-Hernandez, Nury ;

Joseph-Nathan, Pedro .

ORGANIC LETTERS, 2009, 11 (07) :1491-1494

[8] Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase [J].

Cui, Huaqing ;

Ruda, Gian Filippo ;

Carrero-Lerida, Juana ;

Ruiz-Perez, Luis M. ;

Gilbert, Ian H. ;

Gonzalez-Pacanowska, Dolores .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (11) :5140-5149

[9] Anticancer evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives [J].

Evidente, Antonio ;

Kornienko, Alexander .

PHYTOCHEMISTRY REVIEWS, 2009, 8 (02) :449-459

[10] High-Throughput Screening of Natural Products for Cancer Therapy [J].

Harvey, Alan L. ;

Cree, Ian A. .

PLANTA MEDICA, 2010, 76 (11) :1080-1086

← 1 2 3 →