Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: A molecular hybridization approach

被引：43

作者：

Barbosa, Ticiano P. ^{[1
]}

Sousa, Suervy C. O. ^{[1
]}

Amorim, Francianne M. ^{[2
]}

Rodrigues, Yara K. S. ^{[2
]}

de Assis, Priscilla A. C. ^{[1
]}

Caldas, John P. A. ^{[3
]}

Oliveira, Marcia R. ^{[2
,3
]}

Vasconcellos, Mario L. A. A. ^{[1
]}

机构：

[1] Univ Fed Paraiba, Dept Quim, Lab Sintese Organ Med Paraiba LASOM PB, BR-58059900 Joao Pessoa, Paraiba, Brazil

[2] Univ Fed Paraiba, Dept Biol Mol, BR-58059900 Joao Pessoa, Paraiba, Brazil

[3] Univ Fed Paraiba, Lab Tecnol Farmaceut, BR-58059900 Joao Pessoa, Paraiba, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 14期

关键词：

Molecular hybridization; Morita-Baylis-Hillman adducts; Antileishmanial activity; Methyl salicylate; Acryloyl salicylate; BAYLIS-HILLMAN REACTION; ENANTIOSELECTIVE SYNTHESIS; TRYPANOTHIONE REDUCTASE; VISCERAL LEISHMANIASIS; AMPHOTERICIN-B; MECHANISM; SUBSTITUTION; SALICYLATE; INFECTION; ADDUCTS;

D O I：

10.1016/j.bmc.2011.05.055

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 chalcone-like series 1a-1g was efficiently synthesized from Morita-Baylis-Hillman reaction (52-74% yields). Compounds 1a-1g were designed by molecular hybridization based on the anti-inflammatory drug methyl salicylate (3) and the antileishmanial moiety of the Morita-Baylis-Hillman adducts 2a-2g. The 1a-1g compounds were much more actives than precursor series 2a-2g, for example, IC50 = 7.65 mu M on Leishmania amazonensis and 10.14 mu M on Leishmania chagasi (compound 1c) when compared to IC50 = 50.08 mu M on L. amazonensis and 82.29 mu M on L. chagasi (compound 2c). The IC50 values of compound 3 (228.49 mu M on L. amazonensis and 261.45 mu M on L. chagasi) and acryloyl salicylate 4 (108.50 mu M on L. amazonensis and 118.83 mu M on L. chagasi) were determined here, by the first time, on Leishmania. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4250 / 4256

页数：7

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