Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds

被引：193
作者：
Guantai, Eric M. [1 ]
Ncokazi, Kanyile [1 ]
Egan, Timothy J. [1 ]
Gut, Jiri [2 ]
Rosenthal, Philip J. [2 ]
Smith, Peter J. [3 ]
Chibale, Kelly [1 ,4 ]
机构：
[1] Univ Cape Town, Dept Chem, ZA-7701 Rondebosch, South Africa
[2] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA
[3] Univ Cape Town, Div Pharmacol, ZA-7925 Observatory, South Africa
[4] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7701 Rondebosch, South Africa
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 23期
基金：
新加坡国家研究基金会; 美国国家卫生研究院; 英国医学研究理事会;
关键词：
Malaria; Chalcones; Dienones; Triazole; Hybrid compounds; Plasmodium falciparum; Aminoquinolines; Nucleosides; HUMAN MALARIA PARASITES; BETA-HEMATIN FORMATION; PLASMODIUM-FALCIPARUM; CHLOROQUINE; RESISTANCE; PEPTIDOTRIAZOLES; INHIBITORS; ALKYNES; AZIDES; DRUGS;
D O I：
10.1016/j.bmc.2010.10.009
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：
A targeted series of chalcone and dienone hybrid compounds containing aminoquinoline and nucleoside templates was synthesized and evaluated for in vitro antimalarial activity. The Cu(I)-catalyzed cycloaddition of azides and terminal alkynes was applied as the hybridization strategy. Several chalcone-chloroquinoline hybrid compounds were found to be notably active, with compound 8b the most active, exhibiting submicromolar IC50 values against the D10, Dd2 and W2 strains of Plasmodium falciparum. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：8243 / 8256
页数：14
相关论文
共 51 条
[1]   Synthesis and evaluation of 5' alkyl ester prodrugs of zidovudine for directed lymphatic delivery [J].
Bibby, DC ;
Charman, WN ;
Charman, SA ;
Iskander, MN ;
Porter, CJH .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1996, 144 (01) :61-70
[2]   Access to hematin: The basis of chloroquine resistance [J].
Bray, PG ;
Mungthin, M ;
Ridley, RG ;
Ward, SA .
MOLECULAR PHARMACOLOGY, 1998, 54 (01) :170-179
[3]   Rapid diversity-oriented synthesis in microtiter plates for in situ screening of HIV protease inhibitors [J].
Brik, A ;
Muldoon, J ;
Lin, YC ;
Elder, JH ;
Goodsell, DS ;
Olson, AJ ;
Fokin, VV ;
Sharpless, KB ;
Wong, CH .
CHEMBIOCHEM, 2003, 4 (11) :1246-1248
[4]   LICOCHALCONE-A, A NEW ANTIMALARIAL AGENT, INHIBITS IN-VITRO GROWTH OF THE HUMAN MALARIA PARASITE PLASMODIUM-FALCIPARUM AND PROTECTS MICE FROM P-YOELII INFECTION [J].
CHEN, M ;
THEANDER, TG ;
CHRISTENSEN, SB ;
HVIID, L ;
ZHAI, L ;
KHARAZMI, A .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (07) :1470-1475
[5]   The novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo [J].
Chen, M ;
Christensen, SB ;
Zhai, L ;
Rasmussen, MH ;
Theander, TG ;
Frokjaer, S ;
Steffansen, B ;
Davidsen, J ;
Kharazmi, A .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (05) :1327-1333
[6]   Synthesis and in vitro antitubercular activity of a series of quinoline derivatives [J].
de Souza, Marcus V. N. ;
Pais, Karla C. ;
Kaiser, Carlos R. ;
Peralta, Monica A. ;
Ferreira, Marcelle de L. ;
Lourenco, Maria C. S. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (04) :1474-1480
[7]  
Dechy-Cabaret O, 2000, CHEMBIOCHEM, V1, P281, DOI 10.1002/1439-7633(20001117)1:4<281::AID-CBIC281>3.3.CO
[8]  
2-N
[9]   Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity [J].
Domínguez, JN ;
Charris, JE ;
Lobo, G ;
de Domínguez, NG ;
Moreno, MM ;
Riggione, F ;
Sanchez, E ;
Olson, J ;
Rosenthal, PJ .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (06) :555-560
[10]   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
123456