Computer-assisted correlation of structure and biological activity in a set of retinoids

Cancer Res. 1985 Oct;45(10):4741-7.

Abstract

A computer-assisted pattern-recognition system (ADAPT) designed to elucidate structure-activity relationships was applied to a set of retinoids, potentially useful inhibitors of carcinogenesis. A data set of 67 retinoids was used as input to the ADAPT system; their structures were entered, and their 3-dimensional configurations were optimized by a molecular modelling algorithm. Forty of these retinoids were defined as the "more active" class based upon their ability to reverse keratinization in vitamin A-deficient hamster tracheal organ cultures at 10(-10) M or less. The remaining 27 retinoids were defined as the "less active" class due to their lack of ability to elicit this effect at 10(-8) M or more. Thirteen descriptors were generated by ADAPT for each of these retinoids based upon their structures, including: number of ring atoms; double bonds; del Ré sigma charges; and principal moments. Pattern recognition analysis techniques were applied to this data set to determine if information contained in these descriptors could generate a discriminant function equation which could separate more active from less active retinoids, successfully. Computer recognition of more active from less active retinoids was demonstrated by a number of pattern recognition techniques, and the discriminant function could predict correctly the relative activity of retinoids of "unknown" activity in 87% of trials. These results indicate the existence of distinct structure-activity relationships in this set of biologically important molecules.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Computers*
  • Cricetinae
  • Models, Molecular
  • Organ Culture Techniques
  • Retinoids / pharmacology*
  • Software*
  • Structure-Activity Relationship
  • Trachea / drug effects

Substances

  • Retinoids