Prediction and Study of Anticonvulsant Properties of Benzimidazole Derivatives
- Authors: Vasil’ev P.M.1, Kalitin K.Y.1, Spasov A.A.1,2, Grechko O.Y.1, Poroikov V.V.3, Filimonov D.A.3, Anisimova V.A.4
-
Affiliations:
- Volgograd State Medical University
- Volgograd Medical Scientific Center
- V. N. Orekhovich Institute of Biomedical Chemistry
- Institute of Physical and Organic Chemistry, Southern Federal University
- Issue: Vol 50, No 12 (2017)
- Pages: 775-780
- Section: Search for New Drugs
- URL: https://journals.rcsi.science/0091-150X/article/view/244477
- DOI: https://doi.org/10.1007/s11094-017-1530-6
- ID: 244477
Cite item
Abstract
Anticonvulsive activities of some condensed imidazo[1,2-a]benzimidazole derivatives were predicted using PASS software. Benzimidazoles as a class showed promise as sources of anticonvulsants. Several compounds demonstrated various levels of anticonvulsive activity in the corazole-induced seizure model (75 mg/kg, s.c.). The most promising compounds (laboratory codes RU-1205, RU-285, RU-1204, and RU-1203) at a dose of 10 mg/kg (i.p.) showed high levels of anticonvulsive activity comparable with that of reference valproic acid (130 mg/kg, i.p.) at a molar ratio of ~1:30. The Free—Wilson model was used to describe quantitative structure—activity relationships in order to evaluate contributions of substituents or structural fragments to the anticonvulsive activity of the parent structure. Four pharmacophore patterns that favored high anticonvulsive activity among imidazo[1, 2-a]benzimidazole derivatives were found using IT Microcosm.
About the authors
P. M. Vasil’ev
Volgograd State Medical University
Email: chem@folium.ru
Russian Federation, 1 Pavshikh Bortsov Sq., Volgograd, 401131
K. Yu. Kalitin
Volgograd State Medical University
Email: chem@folium.ru
Russian Federation, 1 Pavshikh Bortsov Sq., Volgograd, 401131
A. A. Spasov
Volgograd State Medical University; Volgograd Medical Scientific Center
Email: chem@folium.ru
Russian Federation, 1 Pavshikh Bortsov Sq., Volgograd, 401131; Volgograd, 400131
O. Yu. Grechko
Volgograd State Medical University
Email: chem@folium.ru
Russian Federation, 1 Pavshikh Bortsov Sq., Volgograd, 401131
V. V. Poroikov
V. N. Orekhovich Institute of Biomedical Chemistry
Email: chem@folium.ru
Russian Federation, 10/8 Pogodinskaya St., Moscow, 119121
D. A. Filimonov
V. N. Orekhovich Institute of Biomedical Chemistry
Email: chem@folium.ru
Russian Federation, 10/8 Pogodinskaya St., Moscow, 119121
V. A. Anisimova
Institute of Physical and Organic Chemistry, Southern Federal University
Email: chem@folium.ru
Russian Federation, Rostov-on-Don, 344006