Modeling the anticancer action of some retinoid compounds by making use of the OASIS method.
The powerful OASIS (optimized approach based on structural indices set) approach is applied to the anticancer activity of a series of vitamin A analogs. The best three- and four-variable models obtained via the OASIS technique have correlation coefficients of 0.973 vs. 0.990 and standard deviations s2 = 0.11 and 0.05, respectively. The models incorporate the hydrophobicity factor log P, two geometric parameters (topological indices and/or 3-D steric ones), and the molecular dipole moment. For a set of 15 compounds studied here, the activity measured by ED50 was well correlated by models with approximately equal contribution of the through cell membrane transport and the geometric drug-receptor correspondence while weak nonspecific electronic interaction was also found to play some role. Comparison to previous treatments of this data is given and extension to larger sets is discussed.
M.D. Anderson Cancer Center, Houston, Texas 77030.
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D
Bonchev
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Mountain
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Seitz
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Balaban
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D008956:Models, Chemical; D008968:Molecular Conformation; D011789:Quantum Theory; D012176:Retinoids / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D012176:Retinoids