title: Esters and amides of maslinic acid trigger apoptosis in human tumor cells and alter their mode of action with respect to the substitution pattern at C-28.
abstract: Cancer is one of the most commonly diagnosed diseases worldwide; its mortality rate is high, and there is still a demand for the development of antitumor active drugs. Triterpenoic acids show many pharmacological effects, among them antitumor activity. One of these, maslinic acid-1 is of interest because of its antitumor profile. It is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize a series of esters and amides differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/propidium iodide assay, DNA laddering and cell cycle experiments. Esters containing small-chain, lipophilic residues increased the cytotoxicity whereas amides as well long-chain esters led to a decrease in activity. The antitumor activity seems to be independent from the substitution pattern at position C-28 for esters and amides but alters their mode of action.
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 2, D-06120 Halle (Saale), Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.forename: Elke
authors.initials: E
authors.lastname: Pianowski
authors.forename: René
authors.initials: R
authors.lastname: Csuk
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D004952:Esters; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid
keywords: Antitumor activity; Apoptosis; Maslinic acid; Structure–activity relationships