Synthesis and Pharmacophore Modeling of Naphthoquinone Derivatives with Cytotoxic Activity in Human Promyelocytic Leukemia HL-60 Cell Line

• DOI: 10.1021/jm060849b
• Publication Date: 2007-01-24T14:00:45Z
• Authors: Elisa Pérez-Sacau; Raquel G. Díaz-Pe...; Ana Estévez-Braun; Angel G. Ravelo; Jose M. García-Ca...; Leonardo Pardo; Mercedes Campillo
• Keywords: Naphthoquinone; 1,4-Naphthoquinone

Catalyst/HypoGen pharmacophore modeling approach and three-dimensional quantitative structure−activity relationship (3D-QSAR)/comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to explain the cytotoxic activity of a set 51 natural synthesized naphthoquinone derivatives tested in human promyelocytic leukemia HL-60 cell line. The computational models facilitated identification structural elements ligands that are key for antitumoral properties. four most salient features highly active β-cycled-pyran-1,2-naphthoquinones [0.1 μM < IC50 0.6 μM] hydrogen-bond interactions carbonyl groups at C-1 (HBA1) C-2 (HBA2), interaction oxygen atom pyran ring (HBA3), methyl (HYD) with hydrophobic area receptor. moderately 1,4-naphthoquinone accurately fulfill only three these features. results our study provide valuable tool designing new more potent analogues.