Cytotoxicity evaluation of natural coptisine and synthesis of coptisine from berberine

• Published in: Farmaco (Società chimica italiana : 1989) Vol. 56; no. 5; pp. 403 - 409
• Main Authors: Colombo, Maria Laura, Bugatti, Carlo, Mossa, Andrea, Pescalli, Nicoletta, Piazzoni, Laura, Pezzoni, Gabriella, Menta, Ernesto, Spinelli, Silvano, Johnson, Francis, Gupta, Ramesh C, Dasaradhi, Lakkaraju
• Format: Journal Article Conference Proceeding
• Language: English
• Published: LAUSANNE Elsevier SAS 01.07.2001; Elsevier; Elsevier Science
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Berberine - analogs & derivatives; Berberine - chemical synthesis; Berberine - pharmacology; Biological and medical sciences; Chelidonium majus; Cisplatin - pharmacology; Coptisine; Cytotoxicity; Drug Screening Assays, Antitumor; General pharmacology; Leukemia L1210 - pathology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Protoberberine alkaloids; Science & Technology; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Synthesis; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Europe; Chelidonium majus; Cytotoxicity; Coptisine; Synthesis; Protoberberine alkaloids; synthesis; coptisine; cytotoxicity; protoberberine alkaloids; Antineoplastic agent; Human; Artemia salina; Iminium compounds; Pharmacognosy; Extract; Malignant tumor; In vitro; Biological activity; Medicinal plant; Crustacea; Alkaloid; Folk medicine; Arthropoda; Plant origin; Aromatic compound; Invertebrata; Branchiopoda; Tumor cell; Oxygen nitrogen heterocycle
• ISSN: 0014-827X; 1879-0569
• DOI: 10.1016/S0014-827X(01)01121-1

The crude extract (80% MeOH in water) of Chelidonii herba exhibited very interesting cytotoxicity against brine shrimp ( Artemia salina Leach) nauplii and cultured human tumour cell in vitro, the colon carcinoma HT 29 (144 h treatment). Fractionation of the crude extract and bioassay-guided procedures showed that the cytotoxic and the antitumour activities were concentrated in the basic extract. On the basis of IR, MS and 1H NMR the compound responsible of the cytotoxic activity was determined to be coptisine. Cytotoxicity evaluation of coptisine was next extended to a panel of human and murine cell lines in comparison with the established antitumour drugs mitoxantrone, doxorubicin (Dx) and cisplatin (CDDP). Coptisine was cytotoxic on LoVo and HT 29 and less potent on L-1210, and it was partially crossresistant on the human tumour colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukaemia cell line resistant to CDDP, L-1210/CDDP. Coptisine alkaloid was then synthesised in gram amount from commercial berberine. A four-step synthetic route was elaborated. The overall yield was about 8–10%. The structural identity of synthetic coptisine was verified by IR and NMR methods. A comparison of the cytotoxic effects on the human tumour colon cell line LoVo and on the murine leukaemia L1210 showed, for both natural and synthetic coptisines, a comparable cytotoxic activity more evident against HT 29 cell line and LoVo cell line, while the activity was lower against the L1210 cell line.