Discovery of active site of vinblastine as application of nanotechnology in medicine

Authors

1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran

3 Department of Chemistry, Qom Branch, Islamic Azad University, Qom, Iran

10.7508/nmj.2014.03.006

Abstract

Objective(s):
Vinblastine is antimitotic, anticancer medicine that disturbs normal microtubule formation and favours depolymerisation. Structural study and finding the active site of vinblastine are the targets of this research.
 
Materials and Methods:
Vinblastine was optimized in vacuum and then in different solvents by Density Functional Theory (DFT) method. Nuclear Magnetic Resonance (NMR) shift measurements were made in different solvents by various dielectric constants by Continuous Set of Gauge Transformations (CSGT).  
Results:
The best structure and function of vinblastine was established. The conformational preferences may be attributed to stereoelectronic effects. The results showed that the structure of vinblastine is more stabile in water rather than the other media. The most active atoms of vinblastine were realized by various spectra of vinblastine in different media including vacuum and diverse solvents.  
Conclusion:
Discovery of active site of vinblastine that could bind to tubulin to perform the antimitosis and anticancer effect in process of cell division was accomplished in this investigation. These data can be applicable to study the binding site of vinblastine-tubulin complex.

Keywords


1. Lobert S, Ingram JW, Correia JJ. The thermodynamics of vinca alkaloid-induced tubulin spirals formation. Biophys Chem. 2007; 126: 50-58

2. Biswas BB, Sen K, Choudhury G, Bhattacharyya B. Molecular biology of tubulin: Its interaction with drugs and genomic organization. J Biosci. 1984; 6: 431-457.

3. Martin-Galiano AJ, Oliva MA, Sanz L, Bhattacharyya A, Serna M, Yebenes H, Valpuesta JM, Andreu JM. Bacterial tubulin distinct loop sequences and primitive assembly properties support its origin from a eukaryotic tubulin ancestor. Biol Chem. 2011; 286: 19789-19803.

4. Lobert S, Frankfuter A, Correia JJ. Energetics of vinca alkaloid interactions with tubulin isotypes: Implications for drug efficacy and toxicity. Cell Motil Cytoskel. 1998; 39: 107-121.

5. Mollaamin F, Varmaghani Z, Monajjemi M. Dielectric effect on thermodynamic properties in vinblastine by DFT/Onsager modelling. Phys Chem Liq. 2011; 49: 318-336.

6. Lobert S, Ingram JW, Hill BT, Correia JJ. A comparison of thermodynamic parameters for vinorelbine and vinflunine-induced tubulin self-association by sedimentation velocity. Mol Pharmacol. 1998; 53: 908-915.

7. Dong JG, Bornmann W, Nakanishi K, Berova N. Structural studies of vinblastine alkaloids by exciton coupled circular dichroism. Phytochemistry, 1995; 40: 1821-1824.

8. March NH, Knapp-Mohammady M. The inhomogeneous electron liquid in some bioinorganic assemblies studied by density functional methods. Phys Chem Liq. 2011; 49: 259-269.

9. Monajjemi M, Saeid L, Najafi F, Mollaamin F. Physical properties of active site of tubulin–binding as anticancer nanotechnology investigation. Int J Phys Sci. 2010; 5: 1609-1621.

10. Hehre WJ, Random L, Schleyer PVR, Pople JA. Ab initio molecular orbital theory. Wiley, New York; 1986.

11. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, et al. Gaussian 98. Revision A.7, Gaussian, Inc., Pittsburgh, PA; 1998.

12. Kanakaraju R, Kolandaivel P. Post Hartree–Fock and DFT studies on pyrrole···nitrogen and pyrrole···carbon monoxide molecules. Int j Mol Sci. 2002; 3: 777-789.

13. Lee C, Yang W, Parr GR. Development of the colle-salvetti correlation-energy formula into a functional of the electron density. Phys Rev. 1988; 37: 785-789.

14. Facelli JC (2002). Encyclopedia of Nuclear Magnetic Resonance; D. M.Grant, R. K. Harris, Eds., London: John Wiley & Sons. 9, 323-333.