Application of QSAR models to the search for tubulin inhibitors in a series of derivatives of 1,3-oxazole

Authors

  • I.V. Semenyuta
  • V.V. Kovalishyn
  • S.G. Pilyo
  • V.N. Blagodatnyy
  • Е.P. Trokhimenko
  • V. S. Brovarets
  • L.A. Metelitsa

DOI:

https://doi.org/10.15407/dopovidi2014.12.152

Keywords:

derivatives of 1;3-oxazole, inhibitors, QSAR models, tubulin

Abstract

The study shows the usage of QSAR models for the search for new tubulin inhibitors. The activity of 282 potential tubulin inhibitors on a dataset of 978 derivatives of oxazole and thiazole is predicted. The calculated Tanimoto index value was 0.5–0.76 for 127 compounds, which confirms the similarity of the structures in the training and test sets. The cytotoxic effect of 11 most active compounds was studied on the cell culture Hep-2. Compounds 1, 3, and 4 showed a high activity with LD50 125.0, 31.7, and 62.5 mg/ml, respectively. Their maximum tolerated doses (MTD) are found to be 15.8, 15.8, and 31.7 mg/ml, respectively. The established LD50 and MTD of compounds 1, 3, and 4 allow us to recommend them for the further study as potential anticancer agents.

Downloads

References

Trifonova E. A., Kochetov A. V., Shumnyi V. K. Uspekhi sovrem. biologii, 2000, 120: 395–405.

Green P. J. Annu. Rev. Plant Physiol. Plant Mol. Biol., 1994, 45: 421–445. https://doi.org/10.1146/annurev.pp.45.060194.002225

Hillwig M. S., Liu X., Liu G. et al. J. Exp. Bot., 2010, 61, No 11: 2951–2965. https://doi.org/10.1093/jxb/erq119

Lers A., Sonego L., Green P. J. et al. Plant Physiol., 2006, 142, No 2, 710–721. https://doi.org/10.1104/pp.106.080135

Reymond P., Weber H., Damond M. et al. Plant Cell., 2000, 12: 707–719. https://doi.org/10.1105/tpc.12.5.707

Galiana E., Bonnet P., Conrod S. et al. Plant Physiol., 1997, 115: 1557–1567. https://doi.org/10.1104/pp.115.4.1557

Ohno H., Ehara Y. Tohoku J. Agric. Res., 2005, 55: 99–109.

Trifonova E. A., Sapotsky M. V., Komarova M. L. et al. Plant Cell Rep., 2007, 26: 1121–1126. https://doi.org/10.1007/s00299-006-0298-z

Hellin E., Torrecillas A., Sevilla F. et al. Biol. plant., 1986, 28, No 6: 424–428. https://doi.org/10.1007/BF02885045

Leschinskaya I. B., Balaban N. P., Kapranova M. N. Methods of determining the activity of related enzymes and nucleases. In: Modern methods for studying nucleic acids and nucleases microorganisms, Kazan: KGU, 1980: 53–60 (in Russian).

Sutton B. C., Shaw M. Plant Physiol., 1982, 69, No 1: 205–209. https://doi.org/10.1104/pp.69.1.205

Khramchenkova O. M. Fundamentals of radiobiology, Gomel: UO “GGU im. F. Skoriny”, 2003 (in Russian).

Vanyushun B. F., Bakeeva L. E., Zamyatnina V. A. et al. Int. Rev. Cytol., 2004, 233: 135–179. https://doi.org/10.1016/S0074-7696(04)33004-4

Blank A., McKeon T. A. Proc. Natl. Acad. Sci. USA, 1989, 86: 3169–3173. https://doi.org/10.1073/pnas.86.9.3169

Blank A., McKeon T. A. Plant Physiol., 1991, 97: 1402–1408. https://doi.org/10.1104/pp.97.4.1402

Published

19.03.2025

How to Cite

Semenyuta, I., Kovalishyn, V., Pilyo, S., Blagodatnyy, V., Trokhimenko Е., Brovarets, V. S., & Metelitsa, L. (2025). Application of QSAR models to the search for tubulin inhibitors in a series of derivatives of 1,3-oxazole . Reports of the National Academy of Sciences of Ukraine, (12), 152–157. https://doi.org/10.15407/dopovidi2014.12.152