Betulinic acid derived amides are highly cytotoxic, apoptotic and selective

• Published in: European journal of medicinal chemistry 2020-12, Vol.207, p.112815, Article 112815
• Main Authors: Hoenke, Sophie, Heise, Niels V., Kahnt, Michael, Deigner, Hans-Peter, Csuk, René
• Format: Article
• Language: English
• Subjects: Amides; Amides - chemistry; Amides - pharmacology; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Betulinic acid; Cell Line, Tumor; Cytotoxicity; Drug Interactions; Drug Screening Assays, Antitumor; Humans; Isoquinoline; Mice; NIH 3T3 Cells; Pentacyclic Triterpenes - chemistry; Platanic acid
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2020.112815

Betulinic and platanic acid derived amides were prepared and screened for their cytotoxic activity. All of the compounds were shown to be cytotoxic for a panel of human tumor cell lines, and especially apoptotic betulinic acid derived compounds 6, 8 and 19 showed low EC50 values. Of special interest was a 4-isoquinolinyl amide of 3-O-acetyl-betulinic acid (compound 19), being the most cytotoxic compound of this series and holding EC50 values as low as EC50 = 1.48 μM (A375 melanoma cells) while being significantly less cytotoxic for non-malignant fibroblasts NIH 3T3 with a selectivity index of >91.2. This finding parallels previous results obtained for SAA21, a augustic acid derived compound thus making the 4-isoquinolinyl moiety to a privileged scaffold. [Display omitted] •Betulinic and platanic acid derived amides were prepared and screened (SRB).•All of the compounds were cytotoxic for a panel of human tumor cell lines.•A 4-isoquinolinyl amide 19 showed EC50 = 1.48 μM for A375 melanoma cells.•Compound 19 held selectivity index of >91.2.•The 4-isoquinolinyl amide moiety seems to be a privileged scaffold.