The chemical and biological potential of C ring modified triterpenoids

• Published in: European journal of medicinal chemistry 2014-01, Vol.72, p.84-101
• Main Authors: Siewert, Bianka, Wiemann, Jana, Köwitsch, Alexander, Csuk, René
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - chemical synthesis; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HT29 Cells; Humans; MCF-7 Cells; Mice; Molecular Conformation; NIH 3T3 Cells; Oleanolic Acid - chemical synthesis; Oleanolic Acid - chemistry; Oleanolic Acid - pharmacology; Oleanolic acid acid; Structure-Activity Relationship; Structure–activity relationships; Triterpenes - chemical synthesis; Triterpenes - chemistry; Triterpenes - pharmacology; Triterpenoids; Ursolic Acid
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.11.025

A convenient and elegant route has been developed to separate the natural regioisomers triterpenoids ursolic acid (UA) and oleanolic acid (OA) as well as derivatives thereof. Eleven unknown derivatives of OA were designed, synthesized, and their cytotoxicity was investigated. Further sixteen compounds were prepared to correlate all compounds in a SAR study. It could be shown that C-ring modifications of OA and UA have only a moderate influence onto the cytotoxic activity of the compounds but a significant impact onto the ability to trigger apoptosis in ovarian cancer cells (cell line A2780). C-ring modifications of oleanolic and ursolic acid have only a moderate influence onto the cytotoxic activity of the compounds but the intact presence of this structural element has a significant impact onto the ability to trigger apoptosis in ovarian cancer cells (cell line A2780). [Display omitted] •C ring modified oleanolic, ursolic and maslinic acid derivatives were synthesized.•The compounds showed antitumor activity using different human cancer cell lines.•Many of the compounds are cytotoxic even in a low μmol concentration.•The compounds act by apoptosis.•Small changes in constitution cause tremendous effects in their mode of action.