2. Academic Validation
  3. Lupane and 18α-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Lupane and 18α-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

  • Eur J Med Chem. 2016 Oct 4:121:120-131. doi: 10.1016/j.ejmech.2016.05.029.
Lucie Borkova 1,  Sona Gurska 2,  Petr Dzubak 2,  Renata Burianova 2,  Marian Hajduch 2,  Jan Sarek 2,  Igor Popa 3,  Milan Urban 4
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Faculty of Science, Palacky University Olomouc, 17. listopadu 1192/12, 771 46, Olomouc, Czech Republic.
  • 2 Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
  • 3 Department of Organic Chemistry, Faculty of Science, Palacky University Olomouc, 17. listopadu 1192/12, 771 46, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
  • 4 Department of Organic Chemistry, Faculty of Science, Palacky University Olomouc, 17. listopadu 1192/12, 771 46, Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic. Electronic address: milan.urban@gmail.com.
PMID: 27236068 DOI: 10.1016/j.ejmech.2016.05.029
Abstract

Lupane derivatives containing an electronegative substituent in the position 2 of the skeleton are often cytotoxic, however, the most active compounds are not selective enough. To further study the influence of a substituent in the position 2 in lupane and 18α-oleanane derivatives on their biological properties, we prepared a set of 38 triterpenoid compounds, 19 of them new, most of them substituted in the position 2. From betulin, we obtained 2-bromo dihydrobetulonic acid and 2-bromo allobetulon and their substitutions yielded derivatives with various substituents in the position 2 such as amines, amides, thiols, and thioethers. Nitration of allobetulon and dihydrobetulonic acid gave 2-nitro and 2,2-dinitro derivatives. Fifteen derivatives had IC50 < 50 μM on a chemosensitive CCRF-CEM (acute lymphoblastic leukemia) cell line and were tested on another seven Cancer cell lines including resistant and two non-cancer lines. 2-Amino allobetulin had IC50 4.6 μM and caused significant block of the tumor cells in S and slightly in G2/M transition and caused strong inhibition of DNA and RNA synthesis at 5 × IC50. 2-Amino allobetulin is the most active derivative of 18α-oleanane skeletal type prepared in our research group to date.

Keywords

Activity; Allobetulin; Betulinic acid; Cell cycle; Cytotoxicity; Triterpene.

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