TARGET-DIRECTED SEARCH OF ANTI-VIRULENCE DRUGS


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Abstract

Modern medicine now encounters with problem of the absence of effective antibacterial drugs, which are able to render therapeutic effect on chronic form of infectious process. Thus, the actual objective is to develop essentially new generation of drugs, on the basis of which should lie identification of new bacterial targets playing key role in process of chronization of infection as well as selection of new physiologically active substances, which are able to render highly specific inhibitory effect on selected target. Solving of this objective is possible during realization of new approaches for search and design of new drugs and, first of all, during usage of bioinformatics methods, which enable to identify new biotargets, select most effective chemical compounds-inhibitors and optimize their pharmacological and pharmacokinetic properties. The most promising bacterial target is secretion systems of pathogenic microorganisms participating in realization of their virulent characteristics and playing major role in transition of infectious process in chronic phase. We performed synthesis of and screening for 80 compounds, which allowed to select a range of inhibitors rendering specific target-directed effect on type 3 secretion system of Chlamydia. Obtained data allow to further assess of biological and therapeutic activity of these compounds on developed models of infectious process in vivo .

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МИШЕНЬ-НАПРАВЛЕННЫЙ ПОИСК АНТИВИРУ ЛЕНТНЫХ ЛЕКАРСТВЕННЫХ СРЕДСТВ
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About the authors

N. A Zigangirova

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

E. D Fedina

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

V. V Zorina

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

P. A Bortsov

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

E. A Tokarskaya

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

A. S Karyagina

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

A. V Alekseevsky

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

M. M Krayushkin

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

E. S Zayakin

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

V. N Yarovenko

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

A. L Gintsburg

Gamaleya Research Institute of Epidemiology and Microbiology; Zelinsky Institute of Organic Chemistry; Belozersky Institute of Physicochemical Biology at Lomonosov Moscow State University, Moscow, Russia

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Copyright (c) 2009 Zigangirova N.A., Fedina E.D., Zorina V.V., Bortsov P.A., Tokarskaya E.A., Karyagina A.S., Alekseevsky A.V., Krayushkin M.M., Zayakin E.S., Yarovenko V.N., Gintsburg A.L.

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