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Synthesis and anticancer activity of aminopropoxytriterpenoids

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Abstract

Triterpenoids with aminopropoxy groups in C-28 or C-3 and C-28 positions were synthesized from betulin, erythrodiol, uvaol, oleantriol and betulinic acid N-methylpiperazinylamide by cyanoethylation and the following catalytic hydrogenolysis. Computational estimating activity spectra of the designed compounds pointed out on their probable antineoplastic and proapoptotic activities. Their in vitro cytotoxic activity was evaluated at the National Cancer Institute, USA. Aminopropoxy derivatives of betulin, erythrodiol and oleantriol demonstrated the highest cytotoxic activity toward the most of 60 used tumor cell lines. Bisaminopropoxyerythrodiol revealed in vivo significant antineoplastic activity toward five mouse solid transplantable tumors. The results of in silico investigations and the efficacy of compounds in a broad panel of cell lines in vitro and the activity of bisaminopropoxyerythrodiol on the in vivo tumor models strongly suggest aminopropoxytriterpenoids as promising compounds for further investigation as anticancer agents.

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Acknowledgments

This work was supported by the grant to Russian Foundation for Basic Research (Project № 11-03-12144). We thank National Cancer Institute for screening of compounds 6, 7, 9, 10, 13, 14, 16–18, 20 on human cancer cell lines. Spectroscopic studies were carried out using equipment available at the “Chemistry” User Facilities Center, Ufa Institute of Chemistry of Russian Academy of Sciences.

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Authors and Affiliations

  1. Ufa Institute of Chemistry, Russian Academy of Sciences, 71, pr. Oktyabrya, Ufa, 450054, Russian Federation

    Gulnara V. Giniyatyllina, Irina E. Smirnova & Oxana B. Kazakova

  2. N.N. Blokhin Russian Cancer Research Center, 24, Kashirskoye Shosse, Moscow, 115478, Russian Federation

    Nadejda P. Yavorskaya, Irina S. Golubeva, Olga S. Zhukova, Rujena B. Pugacheva & Galina N. Apryshko

  3. V.N. Orekhovich Institute of Biomedical Chemistry, 10, Pogodinskaya Street, Moscow, 119121, Russian Federation

    Vladimir V. Poroikov

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  1. Gulnara V. Giniyatyllina
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  2. Irina E. Smirnova
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  3. Oxana B. Kazakova
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  6. Olga S. Zhukova
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  7. Rujena B. Pugacheva
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  8. Galina N. Apryshko
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  9. Vladimir V. Poroikov
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Correspondence to Irina E. Smirnova.

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Giniyatyllina, G.V., Smirnova, I.E., Kazakova, O.B. et al. Synthesis and anticancer activity of aminopropoxytriterpenoids. Med Chem Res 24, 3423–3436 (2015). https://doi.org/10.1007/s00044-015-1392-y

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