A COMPARATIVE QSAR STUDY FOR STRUCTURE-CARCINOGENICITY RELATIONSHIP OF COMPOUNDS FROM THECARCINOGENIC POTENCY DATABASE

 

 

Bono Lucic1, Ante Milicevic1, Sonja Nikolic1, Marjan Vracko2, and Nenad Trinajstiæ1

 

1The Rugjer Boskovic Institute, P.O. Box 180, 10002 Zagreb, Croatia;

2National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia

 

 

We modeled carcinogenicity of compounds from the National toxicology program 1990 to 1993 presenting as the carcinogenic potency database. The Carcinogenic Potency Database (CPDB) is a standardized resource of results of chronic, long-term carcinogenesis bioassays. Experimental data are denoted by TD50 for rats and mice and are taken from Environmental Health Perspectives (1995). The set of compounds consists of 86 molecules where 35 molecules have a positive evaluation of carcinogenicity on rats and 35 molecules on mice. We computed the corresponding descriptors using standard computer programs: DRAGON and CODESSA. DRAGON computed 223 descriptors for rats and 226 descriptors for mice. CODESSA computed 171 descriptors for rats and 167 descriptors for mice. In each case we computed fit (descriptive) models (statistical parameters: Rfit, Sfit) and carried out internal (cross) validation using leave-one--out procedure (statistical parameters: Rcv, Scv). In all cases we considered models with one, two, three and four descriptors. The best models are obtained by DRAGON descriptors and our procedure CROMRsel (Lucic, Trinajstic, 1999). Statistical characteristics of a model with 4 descriptors are: (for rat) Rfit=0.775, Sfit=0.518 and Rcv=0.673, Scv=0.636 and (for mice) Rfit=0.838, Sfit=0.448 and Rcv=0.788, Scv=0.507. The CROMRsel model with 3 DRAGON descriptors is comparable to the CODESSA model with 5 descriptors.

 

Relevant Publications

[1] Gold, L.S., Manley, N.B., Slone, T.H., Garfinkel, G.B., Arnes, B.N., Rohrbach, L., Stern, B.R. and Chow, K. Environmental Health Perspectives 103, (1995) 3-122.

[2] Todeschini, R., Consonni, V.: Handbook of molecular descriptors, Wiley-VCH, Weinheim, Germany (2000).