Directed synthesis of potential antitumor substances among derivatives of 3-mercapto-4-(1H-pyrrol-1-yl)-5-cyclohexyl-1,2,4-triazole(4H)
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.
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.
Upmanyu N., Kumar S., Murali-Dhar, Kharya, Shah K., Mishra P. Acta Poloniae Pharmaceutica. Drug Research, 2011, Vol. 68, 2, pp.212-221.
Goyal P. K., Bhandari A., Rana A. C., Jain C. B. International Journal Chem. Tech. Research, 2010, Vol. 2, 4, pp.1992-1997.
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.
Calisir M. M., Kocyigit-Kaymakcioglu B., Uzbek B., Utuk G. E-Journal of Chemistry, 2010, Suppl. 1, Vol. 7, pp.458-464.
Valentina P., Ilango K., Deepthi M., Harusha P., Pavani G. Journal of Pharmaceutical Sciences and Research, 2009, Vol. 1, 2, pp.74-77.
Kshirsagar A., Toraskar M. P., Kulkarni V., Dhanashirez M. S., Kadam V. International Journal Chem. Tech. Research, 2009, Vol. 1, 3, pp.696-701.
Al-Omar M. A. Molecules, 2010, Vol. 15, pp.502-514.
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.
Idhayadhulla A., Kumar R. S., Nasser A. J. A., Manilal A. Der Pharma Chemica, 2011, Vol. 3, 4, pp.210-218.
Joshi S. D., More U. A., Kulkarni V. H. Indian Journal of Pharmaceutical Sciences, 2013, Vol. 75, 3, pp.310-323.
Bijev A. T., Prodanova P. Khimia geterociklicheskih soedinenij – Chemistry of Heterocyclic Compounds, 2007, Vol. 43, 3, pp.306-313.
Azizi N., Khajeh-Amiri A., Ghafuri H., Bolourtchian M., Saidi M. R. Synlett, 2009, pp.2245-2248.
Poroikov V. V. Medicinal Chemistry Research, 2010, Vol. 19 (S1). pp.30.
Shoemaker R. H. Nature Reviews Cancer, 2006, Vol. 6, pp.813-823.
GOST Style Citations
This work is licensed under a Creative Commons Attribution 4.0 International License.
Abbreviated key title: Ž. org. farm. hìm.
ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)