Biopolym. Cell. 2017; 33(3):183-205.
http://dx.doi.org/10.7124/bc.00094F
Bioorganic Chemistry
Investigation of anticancer and anti-parasitic activity of thiopyrano[2,3-d]thiazoles bearing norbornane moiety
1Kryshchyshyn A. P., 1, 2Atamanyuk D. V., 1Kaminskyy D. V., 3Grellier Ph., 1Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Emanine Ltd
    23, A. Matrosova Str., Kyiv, Ukraine, 01103
  3. National Museum of Natural History, UMR 7245 CNRS MCAM, Sorbonne Universités
    CP 52, 57 Rue Cuvier, Paris 75005, France

Abstract

Aim. To study anticancer activity of a series of new thiopyrano[2,3-d]thiazoles with a norbornane fragment in the molecules. The search for trypanocidal properties of target compounds. Methods. Organic synthesis, analytical and spectral methods, pharmacological screening, COMPARE and SAR analysis. Results. Fused thiopyrano[2,3-d]thiazoles bearing the norbornane moiety were synthesized and modified at the C9 and N5 positions of the main core in order to obtain the compounds with a satisfactory pharmacological profile. A number of compounds with significant level of cancer cells growth inhibition were identified; they include a hit-compound N1-(4-chlorophenyl)-2-{2-[6-oxo-5,9-dithia-7-azatetracyclo [9.2.1.02,10.04,8]tetradec-4(8)-en-3-yl]phenoxy}acetamide IId that selectively inhibited Leukemia cell lines at submicromolar concentrations. Moreover, a series of thiopyrano[2,3-d]thiazoles showed a moderate antitrypanosomal activity. Conclusions. New thiopyrano[2,3-d]thiazoles with the norbornane fragment as well as their analogues with different substituents at the N5 and C9 position were designed and synthesized. The compounds showed significant levels of anticancer activity towards the selected cancer cell lines and may be used for further optimization. The compounds with a high antitumor activity inhibited the growth of Trypanosoma brucei brucei in in vitro tests. The combined anticancer and antitrypanosomal effect of compounds is the basis for further modification and search for a possible mode of action of the target compounds.
Keywords: Thiopyrano[2,3-d]thiazoles, norbornane, synthesis, anticancer activity, anti-trypanosomal activity, SAR.
Full text: (PDF, in English)

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