PL EN


Preferences help
enabled [disable] Abstract
Number of results
2002 | 49 | 1 | 157-168
Article title

The analysis of structure-anticancer and antiviral activity relationships for macrocyclic pyridinophanes and their analogues on the basis of 4D QSAR models (simplex representation of molecular structure).

Content
Title variants
Languages of publication
EN
Abstracts
EN
A new 4D-QSAR approach has been considered. For all investigated molecules the 3D structural models have been created and the set of conformers (fourth dimension) have been used. Each conformer is represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry). The investigation of influence of molecular structure of macrocyclic pyridinophanes, their analogues and certain other compounds on anticancer and antiviral (anti-influenza, antiherpes and antiadenovirus) activity has been carried out by means of the 4D-QSAR. Statistic characteristics for QSAR of PLS (partial least squares) models are satisfactory (R = 0.92-0.97; CVR = 0.63-0.83). Molecular fragments increasing and decreasing biological activity were defined. This information may be useful for design and direct synthesis of novel anticancer and antiviral agents.
Publisher

Year
Volume
49
Issue
1
Pages
157-168
Physical description
Dates
published
2002
received
2001-09-10
revised
2002-01-31
accepted
2002-02-10
Contributors
  • I.I Mechnikov Odessa National University, Odessa, Ukraine
  • A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Odessa, Ukraine
  • Ukrainian Mechnikov Research Anti-Plague Institute, Odessa, Ukraine
  • A.V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Odessa, Ukraine
  • Ukrainian Mechnikov Research Anti-Plague Institute, Odessa, Ukraine
  • D.K. Zabolotny Institute of Microbiology and Virology, Kyiv, Ukraine
  • D.K. Zabolotny Institute of Microbiology and Virology, Kyiv, Ukraine
  • Ukrainian Mechnikov Research Anti-Plague Institute, Odessa, Ukraine
  • Ukrainian Mechnikov Research Anti-Plague Institute, Odessa, Ukraine
  • Ukrainian Mechnikov Research Anti-Plague Institute, Odessa, Ukraine
  • I.I Mechnikov Odessa National University, Odessa, Ukraine
  • I.I Mechnikov Odessa National University, Odessa, Ukraine
  • I.I Mechnikov Odessa National University, Odessa, Ukraine
  • University of Mons-Hainaut, Mons, Belgium
References
  • 1. Lozitsky, V.P., Puzis, L.E. & Polyak, R.Ya. (1988) Resistance of mice to reinfection after E-aminocaproic acid treatment of primary influenza virus infection. Acta Virol. 32, 117-122.
  • 2. Dyachenko, N., Nosach, L., Zhovnovataya, V. & Butenko, N. (1994) The effect of some nucleoside analogues on reproduction of adenoviruses. Antiviral Res. 23 (Suppl.1), 121.
  • 3. Fedtchouk, A.S., Veveritsa, P.G., Lozitsky, V.P. & Girlya, Yu.I. (1999) Medical cure of recidiving herpes simplex virus infections by means of proteolysis inhibitors. Antiviral Res. 41, A67.
  • 4. Kuz'min, V.E., Lozitsky, V.P., Kamalov, G.L., Lozitskaya, R.N., Zheltvay, A.I., Fedtchouk, A.S. & Kryzhanovsky, D.N. (2000) The analysis of structure-anticancer activity relationship in a set of macrocyclic 2,6-bis (2- and 4-formylaryloxymethyl) pyridines Schiff bases. Acta Biochim. Polon. 47, 867-875
  • 5. Lozitsky, V.P., Kuz'min, V.E., Artemenko, A.G., Lozitskaya, R.N., Fedtchouk, A.S., Gridina, T.L. & Kryzhanovsky, D.N. (2001) The analysis of structure-anti-influenza relationship on the basis molecular lattice model for macrocyclic piridinophanes and their analogs. Antiviral Res. 50, A85.
  • 6. Fedchuk, A.S., Lozitsky, V.P., Gridina, T.L., Lozytska, R.N., Kamalov, G.L., Vanden Eynde, J.J., Dyachenko, N.S., Nosach, L.N. & Povnitsa, O.Y. (2001) Synthesis and antiviral properties of 2,6- and 3,5-disubstituted pyridines and their analogs. Antiviral Res. 50, A86.
  • 7. Kuz'min, V.E., Lozitsky, V.P., Kamalov, G.L., Lozitskaya, R.N., Zheltvay, A.I., Fedtchouk, A.S., Kryzhanovsky, D.N., Artemenko, A.G. & Kuz'mina, A.V. (2000) The analysis of structure-anticancer activity relationship in a set of macrocyclic pyridinophanes. Intl. Y. Med. Biol. Environ. 28, 75-82.
  • 8. Monks, A., Scudiero, D. & Skehan, P. (1991) Feasibility of high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst. 83, 757-766.
  • 9. Nosach, L. & Dyachenko, N. (1982) Cytopathology of adenoviruses infections; pp. 1-234, Naukova Dumka, Kiev (in Russian).
  • 10. Vedani, A. & Dobler, M. (2000) Multi-dimensional QSAR in drug design. Prog. Drug Res. 55, 105-135.
  • 11. Kuz'min, V.E. (1994) The structure of chiral molecules. Analysis of the conception of configuration and stereoisomerization mechanism. Zh. Phys. Khim. 68, 1037-1043 (in Russian).
  • 12. Kuz'min, V.E. (1995) The homo- and heterochirality of the dissimmetrical tetrahedrons (chiral simplexes). Stereochemical tunneling. Zh. Struct. Khim. 36, 871-878 (in Russian)
  • 13. Kuz'min, V.E., Chelombitko, V.A., Yudanova, I.V., Stelmakh, I.B. & Rublev, I.S. (1998) Stereochemical analysis by simplex representation of molecules. Zh. Struct. Khim. 39, 549-554 (in Russian).
  • 14. Cramer, R.D., Patterson, D.I. & Bunce, J.D. (1988) Comparative molecular field analysis (CoMFA). 1. Effect of shape binding to carrier proteins. J. Am. Chem. Soc. 110, 5959-5967.
  • 15. Seel, M., Turner, D.B. & Wilett, P. (1999) HQSAR - a highly predictive QSAR Technique based on molecular holograms. QSAR,. 18, 245-252.
  • 16. Burkert, U. & Allinger, N.I. (1982) Molecular Mechanics; pp. 1-364 ACS, Washington D.C.
  • 17. Doweyko, A.M. (1988) The hypothetical active site lattice. An approach to modeling active sites from data on inhibitor molecules. J. Med. Chem. 31, 1396-1406.
  • 18. Kuz'min, V.E., Artemenko, A.G., Kovdienko, N.A., Tetko, I.V. & Livingstone, D.J. (2000) Lattice model for QSAR studies. J. Mol. Modeling 6, 517-526.
  • 19. Rännar, S., Lindgren, F., Geladi, P. & Wold, S. (1994) A PLS kernel algorithm for data sets with many variables and fewer objects. Part 1: Theory and algorithm. J. Chemometrics. 8, 111-125.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv49i1p157kz
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.