Repurposing is a drug development strategy that seeks to use existing medications for new indications. In oncology, there is an increased level of activity looking at the use of non-cancer drugs as possible cancer treatments. The Repurposing Drugs in Oncology (ReDO) project has used a literature-based approach to identify licensed non-cancer drugs with published evidence of anticancer activity. Data from 268 drugs have been included in a database (ReDO_DB) developed by the ReDO project. Summary results are outlined and an assessment of clinical trial activity also described. The database has been made available as an online open-access resource (http://www.redo-project.org/db/).
Four main benzylisoquinoline alkaloids were identified in CM2B, i.e. chelidonine, sanguinarine, chelerythrine and protopine, using HPLC-UV. CM2 showed a high cytotoxic activity against PANC-1 (IC50, 20.7 µg/ml) and HT-29 (IC50, 20.6 µg/ml), and a moderate cytotoxic activity against MDA-MB-231 (IC50, 73.9 µg/ml). CM2 as well as CM2B showed a moderate to high cytotoxic activity against the PANC02 cell line (IC50, 34.4 and 36.0 µg/ml). Low to almost no cytotoxic effect was observed on primary endometrium cancer cells PC-EM005, PC-EM002 and on normal fibroblast cells 3T3, when treated with CM2B. Significantly less metastases were counted in mice treated with 1.2 mg/kg CM2B, but not with 3.6 mg/kg Ukrain(TM), compared to the control group. The extract, however, did not affect the weight of the primary tumours.
The extracts of two medicinal plants used in traditional medicine against malaria were characterized by means of an LC-SPE-NMR and LC-MS platform. The structure of a series of major constituents from Bafodeya benna, as well as minor constituents from Ormocarpum kirkii, was determined. Bafodeya benna was found to contain (2R,3R)-taxifolin-3-O-α-L-rhamnoside or astilbin, and its isomers neoastilbin, neoisoastilbin, and isoastilbin, as well as quercetin-3-O-α-L-rhamnoside. From Ormocarpum kirkii, a series of known flavonoids and biflavonoids was obtained, as well as three new compounds, i.e., 7,7′′-di-O-β-D-glu-cosyl-(−)-chamaejasmin, 7-O-β-D-glucosyl-(I-3, II-3)-biliquiritigenin, and isovitexin-(I-3,II-3)-naringenin. The isolated constituents may explain, at least in part, the traditional use against malaria. LC-SPE-NMR, in combination with LC-MS, is a powerful tool for the fast characterization of plant extracts, in order to define priorities at an early stage of a fractionation procedure. In addition, herbal medicinal products can completely be characterized, both with regard to their major as well as their minor constituents.
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