Quantum Pharmacology: New Direction in Materia Medica

1Chekman, IS
1O.O. Bogomolets National Medical University, Kyiv
Nauka innov. 2010, 6(2):29-35
Section: Scientific Basis of Innovation Activity
Language: Ukrainian
On the basis of literature data analysis and own research new directions in quantum pharmacology development are allocated. They are: 1) research of spatial and electronic structure of materia medica molecules; 2) establishment of dependence between chemical structure and pharmacological activity of medicines (QSAR); 3) role of solvent in preparation effect mechanism; 4) definition of pharmacophores of medical products; 5) design of preparations for various diseases treatment de novo development; 6) forecasting of medicine pharmacological activity; 7) protein-ligand interactions between physiologically active substances of preparations and biomolecules. The further development of a new direction in Materia Medica – quantum pharmacology – is to promote more accelerated synthesis of new medical products for treatment of various diseases.
Keywords: forecast of activity of chemical compounds, medical products, pharmacophores, QSAR, quantum pharmacology
1. D'juar M. Teorija molekuljarnyh orbitalej v organicheskoj himii. Moskva: Mir, 1972 [in Russian].
2. Lobaniv V.V., Stryzhak G.Je. Kurs lekcij z teorii' himichnogo zv'jazku ta osnov hemosorbcii'. Kyiv: Nauk. dumka, 2008 [in Ukrainian].
3. Solov'ev M.E., Solov'ev M.M. Komp'juternaja himija. Moskva: Solon-press, 2005 [in Russian].
4. Stepanov N.F. Kvantovaja mehanika i kvantovaja himija. Moskva: Mir, 2001 [in Russian].
5. Chekman I.S. Kvantova farmakologija: stan naukovyh doslidzhen'. Likars'ka sprava. Vrachebnoe delo. 2007. No 8: 3-11 [in Ukrainian].
6. Clary D.C. Quantum chemistry of complex system. Science. 2006. Vol. 314. P. 265-266.
7. Zagorodnyj M.I., Pashkovs'kyj O.A, Puzyrenko A.M. ta in. Kvantovo-himichni aspekty vzajemodii' pentoksyfilinu z aminokyslotamy. Naukovyj visnyk NMU im. O.O. Bogomol'cja. 2006. No 4: 48-53 [in Ukrainian].
8. Nebesna T.Ju., Chekman I.S. Doslidzhennja kvantovohimichnyh vlastyvostej beta-adrenoblokatoriv — atenololu, metoprololu, propranololu. Naukovyj visnyk NMU im. O.O. Bogomol'cja. 2006. No 4: 79-86 [in Ukrainian].
9. Nebesna T.Ju., Zagorodnyj M.I., Jagupova A.S. ta in. Vyv chennja molekuljarnoi' struktury ta kvantovo-himichnyh vlastyvostej acetylcystei'nu. Ukrai'ns'kyj naukovo-medychnyj molodizhnyj zhurnal. 2007. No 1-2: 19-23 [in Ukrainian].
10. Chekman I.S., Kazakova O.O., Nebesna T.Ju. Kvantovo-himichni ta topologichni deskryptory v doslidzhennjah zalezhnosti «struktura-aktyvnist'» (ogljad literatury ta vlasnyh doslidzhen'). Zhurnal Akademii' medychnyh nauk Ukrai'ny. 2008. 14(4): 636-649 [in Ukrainian].
11. HyperChem™, Release 5.1 Pro for Windows, Copyright ©1998 Hypercube, Inc. Internet Download.
12. Stewart J.J.P. MOPAC: A semiempirical molecular orbital program. J. Computer-Aided Molecular Design. 1990. 4(1): 1-105.
13. Stewart J.J.P. Aplicatoin of the PM6 method to modeling proteins. J. Mol. Model. 2009. 15(7): 767–805.
14. Ugliengo P., Viterbo D., Chian G. MOLDRAW: A program for Representing Molecules and Crystal on Personal Computers. Torino University, Release 1.0, Version A.
15. Xidos J. D., Li J., Zhu T. et al. GAMESOL-version 3.1, University of Minnesota, Minneapolis, 2002, based on the General Atomic and Molecular Electronic Structure System (GAMESS).
16. Basak S.C., Mills D., Mumtaz M.M. A quantitative structure-activity relationship (QSAR) study of dermal ab sor ption using theoretical molecular descriptors. SAR and QSAR in Environmental Research. 2007. 18(1-2): 45-55.
17. Basulev B.F., Saidkhodzhaev A.I., Narzullaev S.S. et al. Molecular modeling and QSAR analysis of the esterogenic and terpenoids isolated from Fedula plants. SAR QSAR Environ Res. 2007. 18(7-8): 663–673.
18. Clare B.W., Supuran C.T. A physically interpretable quantum-theoretic QSAR for some carbonic anhydrase inhibitors with diverse aromatic rings, obtained by a new QSAR procedure. Bioorg. Med. Chem. 2005. 13(6): 2197-2211.
19. Popelier P.L., Smith P.J. QSAR models based on quantum topological molecular similarity. Eur. J. Med. Chem. 2006. 41(5): 862-873.
20. Sutherland J.J., O'Brien L.A., Weaver D.F. A comparison of methods modeling quantitative structure – Activity Relationships. J. Med. Chem. 2004. Vol. 47. P. 5541-5554.
21. Tropsha A. Variable selection QSAR modeling, model validation, and virtual screening. An. Rep. Comp. Chem. 2007. Vol. 2. P. 113-168.
22. Zhang L., Zhou P., Yang F. et al. Computer-based QSARs for predicting mixture toxicity of benzene and its derivatives. Chemosphere. 2007. 67(2): 396-401.
23. Miani A., Raugei S., Carloni P. et al. Structure and Raman spectrum of clavulanic acid in aqueous solution. J. Phys. Chem. 2007. Vol. 111. P. 2621-2630.
24. Chekman Y.S., Kazakova O.A., Nebesnaja T.Ju. i dr. Izuchenye kvantovo-farmakologycheskyh svojstv dygoksyna. Dopovidi Nacional'noi' akademii' nauk Ukrai'ny. 2008. No 4: 182-187 [in Russian].
25. Battacharjee A.K., Skanchy D.J., Jenning B. Analysis of stereoelectronic properties, mechanism of action and pharmacophore of synthetic indolo[2,1-b]quinazoline-6,12-dione derivatives in relation to antileishmanial activity using quantum chemical, cyclic voltammetry and 3-DQSAR CATALYST procedures. Bioorg. Med. Chem. 2002. Vol. 10. P. 1979-1989.
26. Alagona G., Ghio C., Monti S. Ab initio modeling of com petitive drug-drug interactions: 5-fluorouracil dimers in the gas phase and in solution. Intern. J. Quant. Chem. 2001. 83(3-4): 128-142.
27. Baker M.L., Jiang W., Wedemeyer W.J. Ab initio modeling of the herpesvirus VP26 core. Comput. Biol. 2006. 2(10): 1632-1636.
28. Sadym A.V., Lagunin A.A., Filimonov D.A., Poroikov V.V. Internet-system for prediction of biological activity spectra of chemical substances. Chim. Pharm. J. 2002. 36(10): 21-26.
29. Bertini I., Fragai M., Giachetti A. Combining in ilico tools and NMR data to validate portein-ligand structural models. Application to matrix metalloproteinases. J. Med. Chem. 2005. Vol. 48. P. 7544-7559.
30. Cornell W.D. Recent evaluations of high throughput docking methods for pharmaceutical leads finding — consensus and caveats. An. Rep. Comp. Chem. 2007. Vol. 2. P. 299-323.
31. Rinaldo D., Philipp D.M., Lippard S.J. et al. Intermediates in dioxygen activation by methane monooxygenase: a QM/MM study. J. Amer. Chem. Soc. 2007. Vol. 129. P. 3135-3147.
32. Wang Y., Cheng J., Qian X. Actions between neonicotinoids and key residues of insect nAChR based on an abquantum chemistry study: Hydrogen bonding and coo pe rative π−π interaction. Bioorg. Med. Chem. 2007. Vol. 15. P. 2624-2630.
33. Saan H.M., Thiel W. QM/MM methods for biomolecular system. Andrew Chem. INT. Ed. Engl. 2009. 48(7):1198-1229.