Geronikaki A., Dearden J., Filimonov D., Galaeva I., Garibova T., Gloriozova T., Krajneva V., Lagunin A., Macaev F., Molodavkin G., Poroikov V., Pogrebnoi S., Shepeli F., Voronina T., Tsitlakidou M., Vlad L.
- Journal of Medicinal Chemistry , 2004
To discover new cognition enhancers, a set of virtually designed synthesizable compounds from
different chemical series was investigated using two computer-aided approaches. One of the
approaches is prediction of biological activity spectra for substances (PASS) and the second is
prediction of to...
To discover new cognition enhancers, a set of virtually designed synthesizable compounds from
different chemical series was investigated using two computer-aided approaches. One of the
approaches is prediction of biological activity spectra for substances (PASS) and the second is
prediction of toxicity, mutagenicity, and carcinogenicity (DEREK). To increase the probability of finding new chemical entities, we investigated a heterogeneous set of highly diverse chemicals including different types of heterocycles: five-membered (thiophenes, thiazoles, imidazoles, oxazoles, pyrroles), six-membered (pyridines, pyrimidines), seven-membered (diazepines, triazepines), fused five+six-membered heterocycles (indoles, benzothiazoles, purines, indolizines, neutral, mesoionic, and cationic azolopyridines). A database including 5494 structures of compounds was created. On the basis of the PASS and DEREK prediction results, eight compounds with the highest probability of cognition-enhancing effect were selected. The
cognition-enhancing activity testing showed that all of the selected compounds had a pronounced
antiamnesic effect and were found to reduce significantly scopolamine-induced amnesia of
passive avoidance reflex (PAR). The action of compounds at doses of 1 and 10 mg/kg caused a
statistically significant increase in latent time of reflex and in the number of animals, which
did not enter the dark chamber when testing the PAR. Therefore, on the basis of computer
prediction, new cognition-enhancing agents were discovered within the chemical series, in which
this activity was not known previously.
Journal of Medicinal Chemistry, 2004, 47 (11), 2870-2876.
