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Vol 45(2011) N 3 p. 517-521; A.L. Zakharenko1, M.V. Sukhanova1, S.N. Khodyreva1, F.N. Novikov2, V.S. Stroylov2, D.K. Nilov2, G.G. Chilov3, V.K. Svedas2,3*, O.I. Lavrik1** Improved Procedure of the Search for Poly(ADP-Ribose) Polymerase-1 Potential Inhibitors with the Use of the Molecular Docking Approach 1Institute of Chemical biology and Fundamental Medicine of Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630090 Russia2Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, 119899 Russia 3Belozersky Institute of Physical and Chemical Biology, Moscow State University, Moscow, 119899 Russia *vytas@belozersky.msu.ru **lavrik@niboch.nsc.ru Received - 2010-12-22; Accepted - 2010-12-30 A search for poly(ADP-ribose) polymerase-1 inhibitors by virtual screening of a chemical compound database and a subsequent experimental verification of their activities have been performed. It was shown that the most efficient method to predict inhibitory properties implies a combinatorial approach joining molecular docking capabilities with structural filtration. Among more than 300 000 low molecular chemical compounds, 9PARP1 inhibitors were revealed; the most active ones, namely, STK031481, STK056130, and STK265022, displayed biological effect at a micromolar concentration (IC50 = 2.0, 1.0, and 2.6 M, respectively). poly(ADP-ribose) polymerase-1, inhibitors of poly(ADP-ribosyl)ation, virtual screening, molecular docking |
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