Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin

Molecules

Volumn 18, Issue 4, 2013, Pages 4526-4543

  Boryczka, Stanisław ^a   Bebenek, Ewa ^a   Wietrzyk, Joanna ^b   Kempińska, Katarzyna ^b   Jastrzebska, Maria ^c   Kusz, Joachim ^c   Nowak, Maria ^c  

^a MEDICAL UNIVERSITY OF SILESIA   (Poland)

^b INSTITUTE OF IMMUNOLOGY AND EXPERIMENTAL THERAPY   (Poland)

^c UNIVERSITY OF SILESIA   (Poland)

Author keywords

Acetylenic betulins; Crystal structure; Cytotoxic activity; Synthesis

Indexed keywords

ANTINEOPLASTIC AGENT; BETULIN; TRITERPENE;

ANIMAL; ARTICLE; CELL PROLIFERATION; CELL STRAIN 3T3; CHEMICAL STRUCTURE; DRUG EFFECT; HUMAN; LEUKEMIA P 388; MOUSE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; BALB 3T3 CELLS; CELL LINE, TUMOR; CELL PROLIFERATION; HUMANS; LEUKEMIA P388; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP; TRITERPENES;

EID: 84876764238     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules18044526     Document Type: Article

References (37)

1. Lowitz, J.T. Uber eine neue, fast benzoeartige substanz der briken. Crell's Chem. Ann. 1788, 1, 312-317.
2. Tolstikov, G.A.; Flekhter, O.B.; Shultz, E.E.; Baltina, L.A.; Tolstikov, A.G. Betulin and its derivatives. Chemistry and biological activity. Chem. Sustain. Develop. 2005, 13, 1-29.
3. Alakurtti S.; Mäkelä, T.; Koskimies, S.; Yli-Kauhaluoma, J. Pharmacological properties of the ubiquitous natural product betulin. Eur. J. Pharm. Sci. 2006, 29, 1-13.
4. Tolstikova, T.G.; Sorokina, I.V.; Tolstikov, G.A.; Tolstikov, A.G.; Flekhter, O.B. Biological activity and pharmacological prospects of lupane terpenoids: II. Semisynthetic lupane derivatives. Russ. J. Bioorg. Chem. 2006, 32, 261-276.
5. Drebushchak, T.N.; Mikhailenko, M.A.; Brezgunova, M.E.; Shakhtshneider, T.P.; Kuznetsova S.A. Crystal structure of betulin ethanol solvate. J. Struct. Chem. 2010, 51, 798-801.
6. Boryczka, S.; Michalik, E.; Jastrzebska, M.; Kusz, J.; Zubko, M.; Bebenek, E. X-ray crystal structure of betulin-DMSO solvate. J. Chem. Crystallogr. 2012, 42, 345-351.
7. Mukherjee, R.; Kumar, V.; Srivastava, S.K.; Agarwal, S.K.; Burman, A.C. Betulinic acid derivatives as anticancer agents: Structure activity relationship. Anticancer Agents Med. Chem. 2006, 6, 271-279.
8. Pisha, E.; Chai, H.; Lee, I.S.; Chagwedera, T.E.; Farnsworth, N.R.; Cordell, G.A.; Beecher, C.W.W.; Fong, H.H.S.; Kinghorn, A.D.; Brown, D.M.; et al. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat. Med. 1995, 1, 1046-1051.
9. Eiznhamer, D.A.; Xu, Z.-Q. Betulinic acid: A promising anticancer candidate. Idrugs 2004, 7, 359-373.
10. Mullauer, F.B.; Kessler, J.H.; Medema, J.P. Betulinic acid, a natural compound with potent anticancer effects. Anticancer Drugs 2010, 21, 215-227.
11. Rzeski, W.; Stepulak, A.; Szymański, M.; Juszczak, M.; Grabarska, A.; Sifringer, M.; Kaczor, J.; Kandefer-Szerszeń, M. Betulin elicits anti-cancer effects in tumour primary cultures and cell lines in vitro. Basic Clin. Pharmacol. Toxicol. 2009, 105, 425-432.
12. Dehelean, C.A.; Feflea, S.; Molnar, J.; Zupko, I.; Soica, C. Betulin as an antitumor agent tested in vitro on A431, HeLa and MCF7, and as an angiogenic inhibitor in vivo in the CAM assay. Nat. Prod. Commun. 2012, 7, 981-985.
13. Alakurtti, S.; Heiska, T.; Kiriazis, A.; Sacerdoti-Sierra, N.; Jaffe, C.L.; Yli-Kauhaluoma, J. Synthesis and anti-leishmanial activity of heterocyclic betulin derivatives. Bioorg. Med. Chem. 2010, 18, 1573-1582.
14. Urban, M.; Vlk, M.; Dzubak, P.; Hajduch, M.; Sarek, J. Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid. Bioorg. Med. Chem. 2012, 20, 3666-3674.
15. Pohjala, L.; Alakurtti, S.; Ahola, T.; Yli-Kauhaluoma, J.; Tammela, P. Betulin-derived compounds as inhibitors of Alphavirus replication. J. Nat. Prod. 2009, 72, 1917-1926.
16. Kommera, H.; Kaluderović, G.N.; Dittrich, S.; Kalbitz, J.; Dräger, B.; Mueller, T.; Paschke, R. Carbamate derivatives of betulinic acid and betulin with selective cytotoxic activity. Bioorg. Med. Chem. Lett. 2010, 20, 3409-3412.
17. Ben-Zvi, Z.; Danon, A. Supplement C2: The Chemistry of Triple Bonded Functional Groups. In The Chemistry of Functional Groups; Patai, S., Ed.; Wiley & Sons: New York, NY, USA, 1994; pp. 739-788.
18. Csuk, R.; Barthel, A.; Schwarz, S.; Kommera, H.; Paschke, R. Synthesis and biological evaluation of antitumor-active γ-butyrolactone substituted betulin derivatives. Bioorg. Med. Chem. 2010, 18, 2549-2558.
19. Kazakova, O.B.; Giniyatullina, G.V.; Yamansarov, E.Y.; Tolstikov, G.A. Betulin and ursolic acid synthetic derivatives as inhibitors of Papilloma virus. Bioorg. Med. Chem. Lett. 2010, 20, 4088-4090.
20. Csuk, R.; Sczepek, R.; Siewert, B.; Nitsche, C. Cytotoxic betulin-derived hydroxypropargylamines trigger apoptosis. Bioorg. Med. Chem. 2013, 21, 425-435.
21. Csuk, R.; Barthel, A.; Kluge, R.; Ströhl, D. Synthesis, cytotoxicity and liposome preparation of 28-acetylenic betulin derivatives. Bioorg. Med. Chem. 2010, 18, 7252-7259.
22. Kazakova, O.B.; Yamansarov, E.Yu.; Spirikhin, L.V.; Yunusov, M.S.; Baikova, I.P.; Kukovinets, O.S.; Musin, R.Z. Effective synthesis and transformations of alkyne betulin derivatives. Russ. J. Bioorg. Chem. 2011, 47, 456-460.
23. Csuk, R.; Barthel, A.; Sczepek, R.; Siewert, B.; Schwarz, S. Synthesis, encapsulation and antitumor activity of new betulin derivatives. Arch. Pharm. Chem. Life Sci. 2011, 1, 37-49.
24. Bori, I.D.; Hung, H.-Y.; Qian, K.; Chen, C.-H.; Morris-Natschke, S.L.; Lee, H.-K. Anti-AIDS agents Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry. Tetrahedron Lett. 2012, 53, 1987-1989.
25. Mól, W.; Matyja, M.; Filip, B.; Wietrzyk, J.; Boryczka, S. Synthesis and antiproliferative activity in vitro of novel (2-butynyl) thioquinolines. Bioorg. Med. Chem. 2008, 16, 8136-8141.
26. Boryczka, S.; Mól, W.; Milczarek, M.; Wietrzyk, J.; Bebenek, E. Synthesis and in vitro antiproliferative activity of novel (4-chloro- and 4-acyloxy-2-butynyl)thioquinolines Med. Chem. Res. 2011, 20, 1402-1410.
27. Lugemwa, F.L.; Huang, F.-Y.; Bentley, M.D.; Mendel, M.J.; Alford, A.R. A Heliothis zea antifeedant from the abundant birchbark triterpene betulin. J. Agric. Food Chem. 1990, 38, 493-496.
28. Deng, Y.; Snyder, J.K. Preparation of a 24-nor-1,4-dien-3-one triterpene derivative from betulin: A new route to 24-nortriterpene analogues. J. Org. Chem. 2002, 67, 2864-2873.
29. Mohammed, I.E.; Choudhary, M.I.; Ali, S.; Anjum, S.; Atta-ur-Rahman. 20(29)-Lupene-3β,28β- diacetate. Acta Crystallogr. 2006, E62, o1352-o1354.
30. Boryczka, S.; Bebenek, E.; Jastrzebska, M.; Kusz, J.; Zubko, M. Crystal structure of betulinic acid-DMSO solvate. Z. Kristallogr. 2012, 227, 379-384.
31. Geran, R.I.; Greenberg, N.H.; Macdonald, M.M.; Schumacher, A.M.; Abott, B.J. Cell culture technical procedures. Cancer Chemother. Rep. 1972, 3, 59-72.
32. Lamberth, C. Alkyne chemistry in crop protection. Bioorg. Med. Chem. 2008, 17, 4047-4063.
33. Gauthier, C.; Legault, J.; Lebrun, M.; Dufour, P.; Pichette, A. Glycosidation of lupine-type triterpenoids as potent in vitro cytotoxic agents. Bioorg. Med. Chem. 2006, 14, 6713-6725.
34. Bodrikov, I.V.; Borisova, N.V.; Chiyanov, A.A.; Kurskii, Y.A.; Fukin, G.K. Vinylic substitution in the reaction of betulin diacetate with tert-butyl hypochlorite. Russ. J. Org. Chem. 2013, 49, 78-82.
35. Oxford Diffraction, CrysAllis CCD and CrysAllis RED, Versions1.171.32.29; Oxford Diffraction Ltd.: Wrocław, Poland, 2008.
36. Sheldrick, G.M. A short history of SHELX. Acta Crystallogr. 2008, A64, 112-122.
37. Wietrzyk, J.; Chodynski, M.; Fitak, H.; Wojdat, E.; Kutner, A.; Opolski, A. Antitumor properties of diastereomeric and geometric analogs of vitamin D3. Anticancer Drugs 2007, 18, 447-457.