Docking and QSAR analysis of 4-(3,5-diphenyl-4,5-dihydro-pyrazol-l-yl)-l,3- thiazol-2(5H)-ones with anticancer activity in vitro

  • D.Ya. Havrylyuk -
  • B.S. Zimenkovsky -
  • I.V. Drapak -
  • V.V. Atamanyuk -
  • R.B. Lesyk -
Keywords: thiazolones-2, antitumor activity, docking, QSAR

Abstract

It is established, that 4-(3,5-diaryl-4,5-dihydro-pyrazol-l-yl)-l,3-thiazol-2(5H)-ones possess cons­iderable antitumor activity in vitro. Docking research (OpenEye) by traditional 4-thiazolidone biotargets (Bcl-2, tubuline, PPARγ receptors) have shown, that positive results of scoring functions are received only to a fragment of protein Bcl-XL molecule. These facts allow to predict the specified mechanism of action for 4-pyrazolinesubstituted 2-thiazolones. As a result of the QSAR-analysis (BuildQSAR) a number of authentic models of linear regress of antitumor activity dependence from molecular descriptors is received, which can be used for preliminary prediction of anticancer activity on a leukemia lines (CCRF, RPMI) for structurally related compounds.

References

1. Gavriluk D.Y., Lesik RB // Pharmacist. . - 2009. - № 3. - P. 51-55.
2. Gavriluk D.Ya., Lesik RB, Matiychuk VS etc. // Journal of Organic and Pharmaceutical Chemistry. - 2006. - Vol. 4. - Vin. 2 (14). - P. 42-44.
3. Zimenkovsky BS, Lesik RB 4-Thiazolidone. Chemistry, physiological action, prospects. Vinnytsia: The New Book, 2004. - 106 p.
4. Alley MS, Scudiero D.A., Monks R.A. et al. / / Cancer Research. - 1988 - Vol. 48. P. 589-601.
5. Atamanyuk D., Zimenkovsky B., Lesyk R. // J. of Sulfur Chemistry. - Vol. 29, No. 2. - 2008. - P.151-162.
6. Carter P.H., Scherle P.A., Muckelbauer J.A. et al. // Proc. Natl. Acad. Sci. U.S.A. - 2001. - Vol. 98. - P.11879-11886.
7. Chengguo Xing, Liangyou Wang, XiaoHu Tang et al. / / Biorganic & Medicinal Chemistry. - 2007. - Vol. 15.-P.2167-2176.
8. De Oliver D.B., Gaudio A.C. // Quant. Struct.-Act. Relat. - 2000. - Vol. 19 (6). - P. 599—601.
9. French K. J., Upson J. J., Keller S. N. et al. // The J. of Pharmacology and Experimental Therapeutics. - 2006. - Vol. 318. P. 596-603.
10. Gampe R.T., Montana V.G., Lambert M.H. et al. // Mol.Cell. - 2000. - Vol. 5. —P. 545—555.
11. Geronikaki A., Eleftheriou P., Vicini P. et al. // J. of Medicinal Chemistry — 2008. - Vol. 51. - P.5221-5228.
12. Grever M.R., Schepartz S.A., Chabner B.A. / / Seminars in Oncology. - 1992 - Vol. 19, No. 6. - P.622-638.
13. Havrylyuk D., Zimenkovsky B., Vasylenko O. et al. / / European J. of Medicinal Chemistry. - 2008. - Vol.44. -P.1396-1404.
14. Heiland S., Ueland P. M. // Cancer Research. - 1983. - Vol. 43. P. 4142-4147.
15. Kemp A. J., Lyons S. D., Christopherson R.L. // J. Biol. Chem. - 1986. - Vol. 261 (32). P. 14891-18895.
16. Lesyk R., Vladzimirska O., Holota S. et al. / / European J. of Medicinal Chemistry. - 2007. - Vol. 42. P.641-648.
17. Lesyk R., Zimenkovsky B., Atamanyuk D. et al. / / Bioorganic & Medicinal Chemistry. - 2006. - Vol. 14. P. 5230-5240.
18. McGann M.R., Almond H.R., Nicholls A. // Biopolimers. - 2003. - Vol. 68. P. 76-90.
19. Oltersdorf T., Elmore S.W., ShoemakerA.R. et al. // Nature. - 2005. - Vol. 435. P. 677-681.
20. Pevarello P., Brasca M.G., Amici R. et al. // J. of Medicinal Chemistry. - 2004. - Vol. 47. P. 3367-3380.
21. Ravelli R.B., Gigant B., Curmi P.A. // Nature. - 2004. - Vol. 428. P. 198-202.
22. Schulz-Gasch T, Stahl M. // J. Mol. Model. - 2003. - Vol. 9. P. 47-57.
23. Schulz-Gasch T., Stahl M. // Drug Discovery Today: Technologies. - 2004. —Vol. 1, No. 3. - P.231-239.
24. Shoemaker R.H. / / Nature Reviews, Cancer. - 2006. P. 813-823.
25. Smith N. F., Hayes A., James K. et al. // Mol. Cancer Ther. - 2006. - Vol. 5 (6). P. 1628-1637.
26. Zheng W., Degterev A., Hsu E. et al. / / Biorganic & Medicinal Chemistry Letters. - 2008. - Vol. 18. P. 4932-4935.
27. http://dtp.nci.nih.gov
28. http://www.hyper.com
29. http://www.rcsb.org/pdb
Published
2020-07-09
How to Cite
Havrylyuk, D., Zimenkovsky, B., Drapak, I., Atamanyuk, V., & Lesyk, R. (2020). Docking and QSAR analysis of 4-(3,5-diphenyl-4,5-dihydro-pyrazol-l-yl)-l,3- thiazol-2(5H)-ones with anticancer activity in vitro. Farmatsevtychnyi Zhurnal, (6), 69-75. Retrieved from https://pharmj.org.ua/index.php/journal/article/view/897
Section
Original Articles

Most read articles by the same author(s)