In vitro antiplasmodial activity of triazole-linked chloroquinoline derivatives synthesized from 7-chloro-N-(prop-2-yn-1-yl)quinolin-4-amine

被引：17
作者：
Taleli, Lebusetsa [1 ]
de Kock, Carmen [2 ]
Smith, Peter J. [2 ]
Pelly, Stephen C. [1 ]
Blackie, Margaret A. L. [1 ]
van Otterlo, Willem A. L. [1 ]
机构：
[1] Univ Stellenbosch, Dept Chem & Polymer Sci, ZA-7602 Matieland, South Africa
[2] Univ Cape Town, Dept Med, Div Pharmacol, ZA-7925 Observatory, South Africa
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 15期
基金：
新加坡国家研究基金会;
关键词：
Antiplasmodial; 4-Aminoquinoline; CuAAC click chemistry; Triazole linkers; Resistance reversal; PLASMODIUM-FALCIPARUM; BIOLOGICAL EVALUATION; ANTIMALARIAL ACTIVITY; HYBRID MOLECULES; CLICK CHEMISTRY; RETAIN ACTIVITY; ANALOGS; RESISTANCE; DESIGN; SERIES;
D O I：
10.1016/j.bmc.2015.06.044
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：
The synthesis and in vitro evaluation of novel triazole-linked chloroquinoline derivatives as potential antiplasmodial agents against Plasmodium falciparum is reported. The 15 synthesized target compounds were obtained by means of a copper(I)-mediated click reaction between a variety of 1,2- and 1,3-azidoamines and 7-chloro-N-(prop-2-yn-1-yl) quinolin-4-amine in moderate to good yields (53-85%). The compounds were screened for antiplasmodial activity against NF54 chloroquine-sensitive and Dd2 chloroquine-resistant strains, alongside chloroquine and artesunate as reference compounds. Six of the test compounds revealed a 3-5 fold increase in antiplasmodial activity against chloroquine-resistant strain Dd2 compared to chloroquine. Among the six compounds with good antiplasmodial activity, a reduced cross-resistance relative to artesunate (>3 fold in comparison to chloroquine) was observed, mainly in derivatives that incorporated chloroquine-resistance reversing pharmacophores. A general trend for reduced chloroquine cross-resistance was also detected among 12 out of the 15 compounds tested. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4163 / 4171
页数：9
相关论文
共 53 条
  • [1] N- and C-acyclic thionuleoside analogues of 1,2,3-triazole
    Al-Masoudi, NA
    Al-Soud, YA
    Abdul-Zahra, A
    [J]. HETEROATOM CHEMISTRY, 2004, 15 (05) : 380 - 387
  • [2] Reversal Agent and Linker Variants of Reversed Chloroquines: Activities against Plasmodium falciparum
    Andrews, Simeon
    Burgess, Steven J.
    Skaalrud, Deborah
    Kelly, Jane Xu
    Peyton, David H.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (02) : 916 - 919
  • [3] SYNTHESIS OF 1,2-AMINOAZIDES - CONVERSION TO UNSYMMETRICAL VICINAL DIAMINES BY CATALYTIC-HYDROGENATION OR REDUCTIVE ALKYLATION WITH DICHLOROBORANES
    BENALIL, A
    CARBONI, B
    VAULTIER, M
    [J]. TETRAHEDRON, 1991, 47 (38) : 8177 - 8194
  • [4] A 3D QSAR pharmacophore model and quantum chemical structure-activity analysis of chloroquine(CQ)-resistance reversal
    Bhattacharjee, AK
    Kyle, DE
    Vennerstrom, JL
    Milhous, WK
    [J]. JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2002, 42 (05): : 1212 - 1220
  • [5] New Compounds Hybrids 1H-1,2,3-Triazole-Quinoline Against Plasmodium falciparum
    Boechat, Nubia
    Ferreira, Maria de Lourdes G.
    Pinheiro, Luiz C. S.
    Jesus, Antonio M. L.
    Leite, Milene M. M.
    Junior, Carlos C. S.
    Aguiar, Anna C. C.
    de Andrade, Isabel M.
    Krettli, Antoniana U.
    [J]. CHEMICAL BIOLOGY & DRUG DESIGN, 2014, 84 (03) : 325 - 332
  • [6] Synthesis, Structure-Activity Relationship, and Mode-of-Action Studies of Antimalarial Reversed Chloroquine Compounds
    Burgess, Steven J.
    Kelly, Jane X.
    Shomloo, Shawheen
    Wittlin, Sergio
    Brun, Reto
    Liebmann, Katherine
    Peyton, David H.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (17) : 6477 - 6489
  • [7] A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum
    Burgess, Steven J.
    Selzer, Audrey
    Kelly, Jane Xu
    Smilkstein, Martin J.
    Riscoe, Michael K.
    Peyton, David H.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (18) : 5623 - 5625
  • [8] Cegielska B, 2009, CHEM ANAL-WARSAW, V54, P807
  • [9] SYNTHESES VIA VINYL SULFONES .18. RAPID ACCESS TO A SERIES OF HIGHLY FUNCTIONALIZED ALPHA,BETA-UNSATURATED CYCLOPENTENONES - A CAVEAT ON AMINOSPIROCYCLIZATION
    CONRAD, PC
    KWIATKOWSKI, PL
    FUCHS, PL
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1987, 52 (04) : 586 - 591
  • [10] Synthesis and Binding Studies of Novel Diethynyl-Pyridine Amides with Genomic Promoter DNA G-Quadruplexes
    Dash, Jyotirmayee
    Waller, Zoe A. E.
    Pantos, G. Dan
    Balasubramanian, Shankar
    [J]. CHEMISTRY-A EUROPEAN JOURNAL, 2011, 17 (16) : 4571 - 4581
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