Synthesis and Pharmacophore Modeling of Naphthoquinone Derivatives with Cytotoxic Activity in Human Promyelocytic Leukemia HL-60 Cell Line
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- 作者：Elisa Pé ; rez-Sacau ; Raquel G. Dí ; az-Peñ ; ate ; Ana Esté ; vez-Braun ; Angel G. Ravelo ; Jose M. Garcí ; a-Castellano ; Leonardo Pardo ; Mercedes Campillo
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：February 22, 2007
- 年：2007
- 卷：50
- 期：4
- 页码：696 - 706
- 全文大小：401K
- 年卷期：v.50,no.4(February 22, 2007)
- ISSN：1520-4804
文摘
Catalyst/HypoGen pharmacophore modeling approach and three-dimensional quantitative structure-activityrelationship (3D-QSAR)/comparative molecular similarity indices analysis (CoMSIA) methods have beensuccessfully applied to explain the cytotoxic activity of a set of 51 natural and synthesized naphthoquinonederivatives tested in human promyelocytic leukemia HL-60 cell line. The computational models havefacilitated the identification of structural elements of the ligands that are key for antitumoral properties. Thefour most salient features of the highly active 
-cycled-pyran-1,2-naphthoquinones [0.1 
M < IC50 < 0.6M] are the hydrogen-bond interactions of the carbonyl groups at C-1 (HBA1) and C-2 (HBA2), the hydrogen-bond interaction of the oxygen atom of the pyran ring (HBA3), and the interaction of methyl groups (HYD)at the pyran ring with a hydrophobic area at the receptor. The moderately active 1,4-naphthoquinonederivatives accurately fulfill only three of these features. The results of our study provide a valuable tool indesigning new and more potent cytotoxic analogues.
-cycled-pyran-1,2-naphthoquinones [0.1 M < IC50 < 0.6M] are the hydrogen-bond interactions of the carbonyl groups at C-1 (HBA1) and C-2 (HBA2), the hydrogen-bond interaction of the oxygen atom of the pyran ring (HBA3), and the interaction of methyl groups (HYD)at the pyran ring with a hydrophobic area at the receptor. The moderately active 1,4-naphthoquinonederivatives accurately fulfill only three of these features. The results of our study provide a valuable tool indesigning new and more potent cytotoxic analogues.