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Virtual screening,synthesis and biological evaluation of DNA intercalating antiviral agents |
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| Authors: | Kyrylo Klimenko Sergey Lyakhov Marina Shibinskaya Alexander Karpenko Gilles Marcou Dragos Horvath Marina Zenkova Elena Goncharova Rinat Amirkhanov Andrei Krysko Sergei Andronati Igor Levandovskiy Pavel Polishchuk Victor Kuz&#x;min Alexandre Varnek |
| Institution: | 1. Laboratoire de Chemoinformatique, (UMR 7140 CNRS/UniStra), Université de Strasbourg, 4, rue B. Pascal, Strasbourg 67000, France;2. A.V. Bogatsky Physico-Chemical Institute of NAS of Ukraine, Lyustdorfskaya doroga, 86, Odessa 65080, Ukraine;3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia;4. Institute of Molecular and Translational Medicine, Palacky University Olomouc, Hněvotínská 1333/5, Olomouc 779 00, Czech Republic;5. Federal University of Kazan, Kremlevskaya str., 18, Kazan, Russia;6. Department of Organic Chemistry, Kiev Polytechnic Institute, Pr. Pobedy 37, 03056 Kiev, Ukraine |
| Abstract: | This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators. This resulted in 12 hits which then were synthesized and tested for antiviral activity against VaV together with 43 compounds earlier studied against VSV. Two compounds displaying high antiviral activity against VaV and low cytotoxicity were selected for further antiviral activity investigations. |
| Keywords: | Antiviral activity Vaccinia virus Structure-activity modeling Virtual screening DNA affinity |
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