[Computer-aided design of polyketides with the required properties].

We propose an approach to rational design of new polyketides with the required spectrum of biological activity. We developed BioGenPharm software for generation of polyketide combinatorial libraries, prediction of activity spectra for the generated structures and selection of molecules with the required properties on the basis of user defined input parameters and selection criteria. For prediction of polyketide activity spectra we used PASS algorithm (http://www.

Rational design of macrolides by virtual screening of combinatorial libraries generated through in silico manipulation of polyketide synthases.

Bacterial secondary metabolites display diverse biological activities, thus having potential as pharmacological agents. Although most of these compounds are discovered by random screening, it is possible to predict and re-design their structures based on the information on their biosynthetic pathways. Biosynthesis of macrolides, governed by modular polyketide synthases (PKS), obeys certain rules, which can be simulated in silico.

Design, synthesis, computational and biological evaluation of new anxiolytics.

New anxiolytics have been discovered by prediction of biological activity with computer programs pass and derek for a heterogeneous set of 5494 highly chemically diverse heterocyclic compounds (thiazoles, pyrazoles, isatins, a-fused imidazoles and others). The majority of tested compounds exhibit the predicted anxiolytic effect. The most potent activity was found in 2-(4-nitrophenyl)-3-(4-phenylpiperazinomethyl)imidazo[1,2-a]pyridine 8, 1-[(4-bromophenyl)-2-oxoethyl]-3-(1,3-dioxolano)-2-indolinone 3, 5-hydroxy-3-methoxycarbonyl-1-phenylpyrazole 5 and 2-(4-fluorophenyl)-3-(4-methylpiperazinomethyl)imidazo[1,2-a]pyridine 7.

Prediction of biological activity spectra for substances: evaluation on the diverse sets of drug-like structures.

The concept of Biological Activity Spectrum served as a basis for developing PASS (Prediction of Activity Spectra for Substances) software product. PASS predicts simultaneously more than 780 pharmacological effects and biochemical mechanisms based on the structural formula of a substance. It may be used for finding new targets (mechanisms) for known pharmaceuticals and for searching new biologically active substances.