Discriminating Drug-Like Compounds by Partition Trees with Quantum Similarity Indices and Graph Invariants.

The search for new drug candidates in databases is of paramount importance in pharmaceutical chemistry. The selection of molecular subsets is greatly optimized and much more promising when potential drug-like molecules are detected a priori. In this work, about one hundred thousand molecules are ranked following a new methodology: a drug/non-drug classifier constructed by a consensual set of classification trees. The classification trees arise from the stochastic generation of training sets, which in turn are used to estimate probability factors of test molecules to be drug-like compounds. Molecules were represented by Topological Quantum Similarity Indices and their Graph Theoretical counterparts. The contribution of the present paper consists of presenting an effective ranking method able to improve the probability of finding drug-like substances by using these types of molecular descriptors.

Diseño y desarrollo de nuevos fármacos contra la malaria / No disponible

Fundamentos: La creciente resistencia de P. falciparum a los fármacos convencionales obliga a la búsqueda de nuevas alternativas, ya terapéuticas, ya preventivas. Un camino prometedor lo ofrecen los análogos de fosfatidilcolina, que interactúan con el metabolismo de los fosfolípidos. En el campo de la prevención, se estudia el diseño de nuevos insecticidas más eficaces. Métodos: Se utilizan índices topológicos para modelar la actividad inhibidora de P. falciparum, in vitro, así como el efecto insecticida, mediante regresión multilineal o análisis lineal discriminante. Resultados: Se mencionan resultados sobresalientes obtenidos en el campo de los antimaláricos ya publicados, y se presenta un trabajo optimización de análogos de fosfatidilcolina. Se proponen modelos dela actividad insecticida contra Anopheles y Culex, y se presentan substancias que han sido seleccionadas por los modelos como potenciales insecticidas. Conclusiones: La topología molecular ofrece una vía, tanto para el diseño de nuevos antimalariales como de agentes activos contra sus vectores (AU)

Grounds: The increasing resistance of P. falciparum to conventional drugs forces the search of new alternatives, either therapeutic, or preventive. A promising way is offered by the phosphatidyl cholineanalogues, which interact with the metabolism of the phospholipids. In the field of the prevention, the design of new more effective insecticides isstudied. Methods: Topological indices are used to model to the inhibiting activity of P. falciparum, in vitro, as well as the insecticide effect, by means of multilinear regression or linear discriminant analysis. Results: Published results obtained in the field of the antimalarial drugs are mentioned, and a new result on optimization of phosphatidyl choline analogues is presented. Models of the insecticide activity against Anopheles and Culex are proposed, and substances selected by the models as potential insecticides are presented. Conclusions: Molecular topology offers a route either, for the design of new antimalarial drugs, or the design of active agents against its vectors (AU)