Relationships between the structure, cytotoxicity and hydrophobicity of quinazoline derivatives by quantitative structure-activity relationship.
Cytotoxicities of 93 quinazoline derivatives against HeLa cells have been determined as the isoeffective concentrations inhibiting, after a single dose, the protein synthesis to 50% of the control amount after 48 h incubation. The dependence of cytotoxicity on hydrophobicity of the studied derivatives has been described using a previously published model-based approach. The studied derivatives are classified into nine classes each forming a smooth hydrophobicity-cytotoxicity curve. Owing to the acceptable agreement between the model and the data it can be inferred that: (1) the compounds except two derivatives bind to the receptors with approximately the same affinity; (2) the criterion for the classification is the different rate of metabolism. The results represent a basis for a rational development of more potent quinazoline derivatives.
Jantová
S
S
Department of Biochemistry and Microbiology, Faculty of Chemical Technology, Slovak Technical University, Bratislava, Slovakia.
Baláz
S
S
Stankovský
S
S
Spirková
K
K
Lukácová
V
V
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D014176:Protein Biosynthesis / Q000187:drug effects; D011799:Quinazolines / Q000737:chemistry* / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship
D011799:Quinazolines; D018336:Receptors, Aryl Hydrocarbon