Directed synthesis of potential antitumor substances among derivatives of 3-mercapto-4-(1H-pyrrol-1-yl)-5-cyclohexyl-1,2,4-triazole(4H)

Authors

  • N. B. Saidov Tajik National University, Tajikistan
  • V. A. Georgiyants National University of Pharmacy, Ukraine
  • A. M. Demchenko Institute of Pharmacology and Toxicology of the AMS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.14.781

Keywords:

3-mercapto-1, 2, 4-triazole, pyrrole, derivatives, synthesis, antitumor action

Abstract

Synthesis of the series of new 4-(1H-pyrrol-1-yl)-5-cyclohexyl-1,2,4-triazole(4H)-3-yl thioacetanilides from 4-amino-5-cyclohexyl-1,2,4-triazole(4H)-3-yl thioacetanilides previously synthesized is described. The target products 3a-z have been obtained by Paal-Knorre pyrrole condensation of the initial aminocompounds 1 with 2,5-dimethoxytetrahydrofuran (2) in the acetic acid medium. The structure of the substances synthesized has been proven by elemental analysis and NMR spectra data. All compounds synthesized contain signals of the cyclohexane system protons as two multiplets in their NMR spectra at 2.39-2.33 ppm (methyne proton) and 1.76-1.13 ppm (cyclohexyl methylene groups protons). Unlike the starting compounds (1) the end products (3a-z) have no signal of 4-aminogroup proton as a singlet in the spectra at 5.87-5.92 ppm. Instead of it, signals of the pyrrole ring are present as two triplets at 7-20-7.17 and 6.32-6.29 ppm. Among activities being more probable for the substances synthesized due to preliminary PASS-prognosis were inhibition of MAO and some enzymes (Pa = 0.554-0.729). Compound (3w) was selected by the National Cancer Institute (NCI) for in vitro screening on different tumour cell lines. As result of this investigation we have noted that, unfortunately, substance 3w is not an effective inhibitor of tumour cells in the dose studied, in particular the growth percent for leukemia cells for more sensitive lines is 68.48 (RPMI-8226); 69.30 (HL-60(TB)); for non-small cell lung cancer – 63.06 (HOP-92); for melanoma – 47.82 (SK-MEL-5); 67.37 (UACC-62); for renal cancer – 56.66 (UO-31). Sensitivity of all cancer cell lines for the colon, CNS, ovarian, prostate and breast cancer was approximately at the control level.

Downloads

Download data is not yet available.

References

  1. Saidov N. B., Georgiyants V. A., Garna N. V. Zhurnal organichnoi ta farmacevtichnoi khimii – Journal of organic and pharmaceutical chemistry, 2013, Vol. 11, 4(44), pp.33-37.
  2. Upmanyu N., Kumar S., Murali-Dhar, Kharya, Shah K., Mishra P. Acta Poloniae Pharmaceutica. Drug Research, 2011, Vol. 68, 2, pp.212-221.
  3. Goyal P. K., Bhandari A., Rana A. C., Jain C. B. International Journal Chem. Tech. Research, 2010, Vol. 2, 4, pp.1992-1997.
  4. Jubie S., Sikdar P., Kalirajan R., Kalirajan R., Gowramma B., Gomathy S., Elango K. Pakistan Journal Pharmaceutical Research, 2011, Vol. 3, 3, pp.511-513.
  5. Calisir M. M., Kocyigit-Kaymakcioglu B., Uzbek B., Utuk G. E-Journal of Chemistry, 2010, Suppl. 1, Vol. 7, pp.458-464.
  6. Valentina P., Ilango K., Deepthi M., Harusha P., Pavani G. Journal of Pharmaceutical Sciences and Research, 2009, Vol. 1, 2, pp.74-77.
  7. Kshirsagar A., Toraskar M. P., Kulkarni V., Dhanashirez M. S., Kadam V. International Journal Chem. Tech. Research, 2009, Vol. 1, 3, pp.696-701.
  8. Al-Omar M. A. Molecules, 2010, Vol. 15, pp.502-514.
  9. Bhat K. S., Poojary B., Prasad D. J., Naik P., Holla B. S. European Journal of Medicinal Chemistry, 2009, Vol. 44, 12, pp.5066-5070.
  10. Idhayadhulla A., Kumar R. S., Nasser A. J. A., Manilal A. Der Pharma Chemica, 2011, Vol. 3, 4, pp.210-218.
  11. Joshi S. D., More U. A., Kulkarni V. H. Indian Journal of Pharmaceutical Sciences, 2013, Vol. 75, 3, pp.310-323.
  12. Bijev A. T., Prodanova P. Khimia geterociklicheskih soedinenij – Chemistry of Heterocyclic Compounds, 2007, Vol. 43, 3, pp.306-313.
  13. Azizi N., Khajeh-Amiri A., Ghafuri H., Bolourtchian M., Saidi M. R. Synlett, 2009, pp.2245-2248.
  14. Poroikov V. V. Medicinal Chemistry Research, 2010, Vol. 19 (S1). pp.30.
  15. Shoemaker R. H. Nature Reviews Cancer, 2006, Vol. 6, pp.813-823.

Downloads

Published

2014-03-06

How to Cite

(1)
Saidov, N. B.; Georgiyants, V. A.; Demchenko, A. M. Directed Synthesis of Potential Antitumor Substances Among Derivatives of 3-Mercapto-4-(1H-Pyrrol-1-Yl)-5-Cyclohexyl-1,2,4-triazole(4H). J. Org. Pharm. Chem. 2014, 12, 43-46.

Issue

Vol. 12 No. 1(45) (2014)

Section

Original Researches

License

Copyright (c) 2014 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors publishing their works in the Journal of Organic and Pharmaceutical Chemistry agree with the following terms:

1. Authors retain copyright and grant the journal the right of the first publication of the work under Creative Commons Attribution License allowing everyone to distribute and re-use the published material if proper citation of the original publication is given.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book) providing proper citation of the original publication.

3. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on authors’ personal websites) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).