title: Lupane and 18α-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells.
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.
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University Olomouc, 17. listopadu 1192/12, 771 46, Olomouc, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Borkova
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
authors.forename: Sona
authors.initials: S
authors.lastname: Gurska
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Dzubak
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Burianova
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
authors.forename: Marian
authors.initials: M
authors.lastname: Hajduch
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sarek
authors.affiliation: 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.
authors.forename: Igor
authors.initials: I
authors.lastname: Popa
authors.affiliation: 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.
authors.forename: Milan
authors.initials: M
authors.lastname: Urban
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D009696:Nucleic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology; D053978:Pentacyclic Triterpenes
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D009696:Nucleic Acids; D009828:Oleanolic Acid; D014315:Triterpenes; C413246:oleanane; C480546:lupane; D053978:Pentacyclic Triterpenes
keywords: Activity; Allobetulin; Betulinic acid; Cell cycle; Cytotoxicity; Triterpene