新型查耳酮类似物的设计、合成及抗利什曼原虫体外活性：一种分子杂交方法。
Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: a molecular hybridization approach.
机构信息
Laboratório de Síntese Orgânica Medicinal da Paraíba, Departamento de Química, Universidade Federal da Paraíba, Campus I, João Pessoa, PB 58059-900, Brazil.
出版信息
Bioorg Med Chem. 2011 Jul 15;19(14):4250-6. doi: 10.1016/j.bmc.2011.05.055. Epub 2011 Jun 1.
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, IC(50)=7.65 μM on Leishmania amazonensis and 10.14 μM on Leishmania chagasi (compound 1c) when compared to IC(50)=50.08 μM on L. amazonensis and 82.29 μM on L. chagasi (compound 2c). The IC(50) values of compound 3 (228.49 μM on L. amazonensis and 261.45 μM on L. chagasi) and acryloyl salicylate 4 (108.50 μM on L. amazonensis and 118.83 μM on L. chagasi) were determined here, by the first time, on Leishmania.
查尔酮类化合物 1a-1g 是通过 Morita-Baylis-Hillman 反应（产率 52-74%）高效合成的。化合物 1a-1g 是基于抗炎药物水杨酸甲酯（3）和 Morita-Baylis-Hillman 加合物 2a-2g 的抗利什曼原虫部分，通过分子杂交设计的。与前体系列 2a-2g 相比，化合物 1a-1g 具有更高的活性，例如，对 Leishmania amazonensis 的 IC50=7.65 μM，对 Leishmania chagasi 的 IC50=10.14 μM（化合物 1c），而对 Leishmania amazonensis 的 IC50=50.08 μM，对 Leishmania chagasi 的 IC50=82.29 μM（化合物 2c）。化合物 3（对 Leishmania amazonensis 的 IC50=228.49 μM，对 Leishmania chagasi 的 IC50=261.45 μM）和丙烯酰基水杨酸酯 4（对 Leishmania amazonensis 的 IC50=108.50 μM，对 Leishmania chagasi 的 IC50=118.83 μM）的 IC50 值，也是首次在利什曼原虫中测定的。
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