Antiplasmodial and antitumor activity of dihydroartemisinin analogs derived via the aza-Michael addition reaction

被引：22
作者：
Feng, Tzu-Shean [1 ,2 ]
Guantai, Eric M. [3 ]
Nell, Margo J. [4 ]
van Rensburg, Constance E. J. [4 ]
Hoppe, Heinrich C. [2 ]
Chibale, Kelly [1 ,5 ]
机构：
[1] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa
[2] Univ Cape Town, Div Pharmacol, ZA-7925 Observatory, South Africa
[3] Univ Nairobi, Div Pharmacol, Sch Pharm, Nairobi, Kenya
[4] Univ Pretoria, Dept Pharmacol, ZA-0028 Hatfield, South Africa
[5] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 10期
基金：
英国医学研究理事会; 新加坡国家研究基金会;
关键词：
Anticancer; Antiplasmodial; Aza-Michael addition reaction; Chloroquinoline; Dihydroartemisinin; ANTIMALARIAL ARTESUNATE; FALCIPARUM-MALARIA; IN-VITRO; ARTEMISININ; DRUGS; 4-AMINOQUINOLINES; CHLOROQUINE; DERIVATIVES; INHIBITION; RESISTANCE;
D O I：
10.1016/j.bmcl.2011.03.090
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of dihydroartemisinin derivatives were synthesized via an aza-Michael addition reaction to a dihydroartemisinin-based acrylate and were evaluated for antiplasmodial and antitumor activity. The target compounds showed excellent antiplasmodial activity, with dihydroartemisinin derivatives 5, 7, 9 and 13 exhibiting IC50 values of <= 10 nM against both D10 and Dd2 strains of Plasmodium falciparum. Derivative 4d was the most active against the HeLa cancer cell line, with an IC50 of 0.37 mu M and the highest tumor specificity. (C) 2011 Elsevier Ltd. All rights reserved.
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收藏
页码：2882 / 2886
页数：5
相关论文
共 28 条
[1]   Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue [J].
Biot, C ;
Glorian, G ;
Maciejewski, LA ;
Brocard, JS ;
Domarle, O ;
Blampain, G ;
Millet, P ;
Georges, AJ ;
Abessolo, H ;
Dive, D ;
Lebibi, J .
JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (23) :3715-3718
[2]   PITFALLS IN A DISCOVERY - CHRONICLE OF CHLOROQUINE [J].
COATNEY, GR .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1963, 12 (02) :121-+
[3]   Antimalarials: Synthesis of 4-aminoquinolines that circumvent drug resistance in malaria parasites [J].
De, DY ;
Byers, LD ;
Krogstad, DJ .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1997, 34 (01) :315-320
[4]   Structure-activity relationships for antiplasmodial activity among 7-substituted 4-aminoquinolines [J].
De, DYD ;
Krogstad, FM ;
Byers, LD ;
Krogstad, DJ .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (25) :4918-4926
[5]   Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate [J].
Dell'Eva, R ;
Pfeffer, U ;
Vené, R ;
Anfosso, L ;
Forlani, A ;
Albini, A ;
Efferth, T .
BIOCHEMICAL PHARMACOLOGY, 2004, 68 (12) :2359-2366
[6]   Artemisinin Resistance in Plasmodium falciparum Malaria. [J].
Dondorp, Arjen M. ;
Nosten, Francois ;
Yi, Poravuth ;
Das, Debashish ;
Phyo, Aung Phae ;
Tarning, Joel ;
Lwin, Khin Maung ;
Ariey, Frederic ;
Hanpithakpong, Warunee ;
Lee, Sue J. ;
Ringwald, Pascal ;
Silamut, Kamolrat ;
Imwong, Mallika ;
Chotivanich, Kesinee ;
Lim, Pharath ;
Herdman, Trent ;
An, Sen Sam ;
Yeung, Shunmay ;
Singhasivanon, Pratap ;
Day, Nicholas P. J. ;
Lindegardh, Niklas ;
Socheat, Duong ;
White, Nicholas J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (05) :455-467
[7]   Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells [J].
Efferth, T ;
Davey, M ;
Olbrich, A ;
Rücker, G ;
Gebhart, E ;
Davey, R .
BLOOD CELLS MOLECULES AND DISEASES, 2002, 28 (02) :160-168
[8]  
Efferth T, 2001, INT J ONCOL, V18, P767
[9]   Structure-function relationships in aminoquinolines:: Effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of β-hematin formation, and antiplasmodial activity [J].
Egan, TJ ;
Hunter, R ;
Kaschula, CH ;
Marques, HM ;
Misplon, A ;
Walden, J .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (02) :283-291
[10]  
Ferrer R., 2009, Scientia Pharmaceutica, V77, P725
123