Structure-activity relationships of antileishmanial and antimalarial chalcones

被引:249
|
作者
Liu, M
Wilairat, P
Croft, SL
Tan, ALC
Go, ML
机构
[1] Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore
[2] Mahidol Univ, Dept Biochem, Bangkok 10400, Thailand
[3] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
[4] Natl Univ Singapore, Inst Cell & Mol Biol, Singapore 117609, Singapore
关键词
D O I
10.1016/S0968-0896(03)00233-5
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 series of oxygenated chalcones which have been evaluated earlier for antimalarial activity (Plasmodium falciparum K1) were tested for antileishmanial activity against Leishmania donovani amastigotes. A comparison of structure-activity relationships reveal that different physicochemical and structural requirements exist for these two activities. Antileishmanial activity is associated with less lipophilic chalcones, in particular those with 4'-hydroxyl-substituted B rings and hetero/polyaromatic A rings. In contrast, chalcones with good antimalarial activity have alkoxylated B rings and electron-deficient A rings. Visualization of the steric and electrostatic fields generated from comparative molecular field analysis (CoMFA) indicate that the ring A of chalcones make a more significant contribution to antileishmanial activity while both rings A and B are important for antimalarial activity. Despite different requirements, two alkoxylated chalcones (8, 19) were identified which combined good antimalarial and antileishmanial activities. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:2729 / 2738
页数:10
相关论文
共 50 条
  • [21] Synthetic chalcones, flavanones, and flavones as antitumoral agents:: Biological evaluation and structure-activity relationships
    Cabrera, Mauricio
    Simoens, Macarena
    Falchi, Gabriela
    Lavaggi, M. Laura
    Piro, Oscar E.
    Castellano, Eduardo E.
    Vidal, Anabel
    Azqueta, Amaia
    Monge, Antonio
    de Cerain, Adela Lopez
    Sagrera, Gabriel
    Scoane, Gustavo
    Cerecetto, Hugo
    Gonzalez, Mercedes
    BIOORGANIC & MEDICINAL CHEMISTRY, 2007, 15 (10) : 3356 - 3367
  • [22] Structure-activity relationships of some indolo[3,2-c]quinolines with antimalarial activity
    Go, ML
    Ngiam, TL
    Tan, ALC
    Kuaha, K
    Wilairat, P
    EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 6 (01) : 19 - 26
  • [23] Modeling structure-activity relationships of prodiginines with antimalarial activity using GA/MLR and OPS/PLS
    de Campos, Luana Janaina
    de Melo, Eduardo Borges
    JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2014, 54 : 19 - 31
  • [24] STRUCTURE-ACTIVITY RELATIONSHIPS
    MORLEY, JS
    GASTROENTEROLOGY, 1969, 56 (04) : 826 - &
  • [25] STRUCTURE-ACTIVITY RELATIONSHIPS
    MORLEY, JS
    FEDERATION PROCEEDINGS, 1968, 27 (06) : 1314 - +
  • [26] STRUCTURE-ACTIVITY RELATIONSHIPS
    SEXTON, WA
    JOURNAL OF PHARMACY AND PHARMACOLOGY, 1958, 10 (08) : 465 - 482
  • [27] Antimalarial activity of ferrocenyl chalcones
    Wu, X
    Wilairat, P
    Go, ML
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (17) : 2299 - 2302
  • [28] Synthesis and structure-activity relationships of antimalarial 4-oxo-3-carboxyl quinolones
    Zhang, Yiqun
    Guiguemde, W. Armand
    Sigal, Martina
    Zhu, Fangyi
    Connelly, Michele C.
    Nwaka, Solomon
    Guy, R. Kiplin
    BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (07) : 2756 - 2766
  • [29] Antileishmanial and antimalarial chalcones: Synthesis, efficacy and cytotoxicity of pyridinyl and naphthalenyl analogs
    Gutteridge, C. E.
    Vo, J. V.
    Tillett, C. B.
    Vigilante, J. A.
    Dettmer, J. R.
    Patterson, S. L.
    Werbovetz, K. A.
    Capers, J.
    Nichols, D. A.
    Bhattacharjee, A. K.
    Gerena, L.
    MEDICINAL CHEMISTRY, 2007, 3 (02) : 115 - 119
  • [30] Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships
    Mendoza, Adela
    Perez-Silanes, Silvia
    Quiliano, Miguel
    Pabon, Adriana
    Galiano, Silvia
    Gonzalez, German
    Garavito, Giovanny
    Zimic, Mirko
    Vaisberg, Abraham
    Aldana, Ignacio
    Monge, Antonio
    Deharo, Eric
    EXPERIMENTAL PARASITOLOGY, 2011, 128 (02) : 97 - 103