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Keywords = Laser trilobum cultivation

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11 pages, 1010 KiB  
Article
Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8-O-(12-Aminododecanoyl)-8-O-Debutanoylthapsigargin
by Tomáš Zimmermann, Pavel Drašar, Silvie Rimpelová, Søren Brøgger Christensen, Vladimir A. Khripach and Michal Jurášek
Biomolecules 2020, 10(12), 1640; https://doi.org/10.3390/biom10121640 - 5 Dec 2020
Cited by 11 | Viewed by 4062
Abstract
In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces [...] Read more.
In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum, which contains a structurally related sesquiterpene lactone, trilobolide (Tb), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin. Full article
(This article belongs to the Collection Pharmacology of Medicinal Plants)
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