title: Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds.
abstract: The betulinic acid-derived hydroxamates 5-18, the amides 19-24, and betulin-derived bis-carbamates 25-28 as well as the carbamates 31-40 and 44-48 were prepared and evaluated for their antiproliferative activity in a photometric sulforhodamine B (SRB) assay against several human cancer cell lines and nonmalignant mouse fibroblasts (NIH 3T3). While for 3-O-acetyl hydroxamic acid 5 EC50 values as low as EC50 = 1.3 μM were found, N,O-bis-alkyl substituted hydroxamates showed lowered cytotoxicity (EC50 = 16-20 μM). In general, hydroxamic acid derivatives showed only reduced selectivity for tumor cells, except for allyl substituted compound 13 (EC50 = 5.9 μM for A2780 human ovarian carcinoma cells and EC50 > 30 μM for nonmalignant mouse fibroblasts). The cytotoxicity of betulinic acid derived amides 19-24 and of betulin derived bis-carbamates 25-28 was low, except for N-ethyl substituted 25. Hexyl substituted 39 showed EC50 = 5.6 μM (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined.
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Wiemann
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heller
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Perl
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Kluge
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Ströhl
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address: rene.csuk@chemie.uni-halle.de.
authors.forename: René
authors.initials: R
authors.lastname: Csuk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D053978:Pentacyclic Triterpenes; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D003603:Cytotoxins; D006877:Hydroxamic Acids; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid
keywords: Betulin; Betulinic acid; Carbamates; Hydroxamates; Triterpenes; Tumor cells