The OASIS concept for predicting the biological activity of chemical compounds

The existing QSAR approaches are critically assessed. The OASIS methodology is outlined as a generalization of the Hansch method. A large set of calculable geometric (topological, steric) and electronic indices is used to characterize molecular structure. The number of descriptors is reduced stepwise in a preliminary screening procedure, thus strongly diminishing the risk of a chance correlation. The non-formal parameters included in the ultimate mathematical model provide opportunities for shedding light on the biological interaction mechanism. Implemented as an IBM PC pack, the OASIS system is applied to various series of drugs, arriving at successful regression models.

[1]  Y. Martin,et al.  A practitioner's perspective of the role of quantitative structure-activity analysis in medicinal chemistry. , 1981, Journal of medicinal chemistry.

[2]  Lee Griffiths,et al.  Approaches to charge calculations in molecular mechanics , 1982 .

[3]  Quantitative structure-activity relationships of purines I: Choice of parameters and prediction of pKa values. , 1981, Journal of pharmaceutical sciences.

[4]  S H Unger,et al.  "Aromatic" substituent constants for structure-activity correlations. , 1973, Journal of medicinal chemistry.

[5]  A. Cammarata,et al.  Pattern recognition II: Investigation of structure--activity relationships. , 1977, Journal of pharmaceutical sciences.

[6]  L. Hall,et al.  Molecular connectivity in chemistry and drug research , 1976 .

[7]  C. Hansch,et al.  On the structure of medicinal chemistry. , 1976, Journal of medicinal chemistry.

[8]  Michael J. S. Dewar,et al.  The molecular orbital theory of organic chemistry , 1969 .

[9]  J. Gasteiger,et al.  ITERATIVE PARTIAL EQUALIZATION OF ORBITAL ELECTRONEGATIVITY – A RAPID ACCESS TO ATOMIC CHARGES , 1980 .

[10]  S C Basak,et al.  Comparative study of lipophilicity versus topological molecular descriptors in biological correlations. , 1984, Journal of pharmaceutical sciences.

[11]  C. Hansch,et al.  p-σ-π Analysis. A Method for the Correlation of Biological Activity and Chemical Structure , 1964 .

[12]  A. Cammarata,et al.  Quantum chemical approach to structure-activity relationships of tetracycline antibiotics. , 1971, Journal of pharmaceutical sciences.

[13]  W. Todd Wipke,et al.  Computer representation and manipulation of chemical information , 1974 .

[14]  Alexandru T. Balaban,et al.  Chemical graphs , 1979 .

[15]  S. Unger.  Molecular Connectivity in Structure–activity Analysis , 1987 .

[16]  I. Gutman,et al.  Graph theory and molecular orbitals. Total φ-electron energy of alternant hydrocarbons , 1972 .

[17]  Danail Bonchev,et al.  Unique description of chemical structures based on hierarchically ordered extended connectivities (HOC procedures). VIII. General principles for computer implementation , 1985 .

[18]  M. Randic.  Characterization of molecular branching , 1975 .

[19]  J. Topliss,et al.  Chance factors in studies of quantitative structure-activity relationships. , 1979, Journal of medicinal chemistry.

[20]  Danail Bonchev,et al.  Unique description of chemical structures on hierarchically ordered extended connectivities (HOC procedures). II. Mathematical proofs for the HOC algorithm , 1985 .

[21]  Robert W. Taft,et al.  Polar and Steric Substituent Constants for Aliphatic and o-Benzoate Groups from Rates of Esterification and Hydrolysis of Esters1 , 1952 .

[22]  R. Daudel,et al.  Molecular orbital calculations on some nitrogen derivatives of conjugated hydrocarbons: base strength of benzacridines and their amino derivatives. , 1972, Journal of pharmaceutical sciences.

[23]  M. Dewar,et al.  Ground States of Molecules. 38. The MNDO Method. Approximations and Parameters , 1977 .

[24]  Walter Thiel.  The MNDOC method, a correlated version of the MNDO model , 1981 .

[25]  Alexandru T. Balaban,et al.  Topological indices based on topological distances in molecular graphs , 1983 .

[26]  A. Balaban,et al.  Unique description of chemical structures based on hierarchically ordered extended connectivities (HOC procedures). I. Algorithms for finding graph orbits and canonical numbering of atoms , 1985 .

[27]  R. Pariser.  An Improvement in the π‐Electron Approximation in LCAO MO Theory , 1953 .

[28]  Ivan V. Stankevich,et al.  Topological Indices in Organic Chemistry , 1988 .

[29]  L. Kier.  Quantitation of solvent polarity based on molecular structure. , 1981, Journal of pharmaceutical sciences.

[30]  H. Wiener.  Structural determination of paraffin boiling points. , 1947, Journal of the American Chemical Society.

[31]  A. Balaban.  Chemical applications of graph theory , 1976 .

[32]  H. Hosoya.  Topological Index. A Newly Proposed Quantity Characterizing the Topological Nature of Structural Isomers of Saturated Hydrocarbons , 1971 .

[33]  D. Bonchev,et al.  Modeling the Interaction of Small Organic Molecules with Biomacromolecules (the Oasis Approach). V. Toxicity of Phenols to Algae “Lemna Minor” , 1988 .

[34]  A. Verloop,et al.  Development and Application of New Steric Substituent Parameters in Drug Design , 1976 .

[35]  A. Leo,et al.  Substituent constants for correlation analysis in chemistry and biology , 1979 .

[36]  S. Free,et al.  A MATHEMATICAL CONTRIBUTION TO STRUCTURE-ACTIVITY STUDIES. , 1964, Journal of medicinal chemistry.