ABSTRACT

Abstract ................................................................................................. 226 21.1 Introduction ................................................................................ 226 21.2 Experimental Part ....................................................................... 227 21.3 Results and Discussion .............................................................. 231 21.4 Conclusions ................................................................................ 242 Keywords .............................................................................................. 243 References ............................................................................................. 243

ABSTRACT

Some structural properties characteristics for highly, medium and low effective antitumor compounds are revealed using the computer system SARD-21 (Structure Activity Relationship and Design) and the degree of their influence on cancer cells of hepatoma, cervix and prostate is investigated. Basing on the data received two models of prognosticating interval levels of antitumor activity of sulfur, nitrogen, silicon and oxygen containing heterocyclic compounds with 80% reliability level are constructed by two recognition methods. The revealed structural regularities may be used for constructing highly active antitumor compounds. Additionally we have performed GUSAR (General Unrestricted Structure Activity Relationships) analysis of 30 quinazoline derivatives reported as thymidylate synthetase inhibitors. A robust, statistically sound and thoroughly validated consensus model is obtained. The six parametric model has the following statistical characteristics N=30, R2=0.926, F=34.093, SD=0.247, Q2=0.884, V=6. The GUSAR analysis provides the idea of regarding contribution of each atom in deciding the binding with thymidylate synthetase.