Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8-O-(12-Aminododecanoyl)-8-O-Debutanoylthapsigargin

T. Zimmermann, P. Drašar, S. Rimpelová, SB. Christensen, VA. Khripach, M. Jurášek

. 2020 ; 10 (12) : . [pub] 20201205

Language English Country Switzerland

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21019679

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21019679
003      
CZ-PrNML
005      
20210830101250.0
007      
ta
008      
210728s2020 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/biom10121640 $2 doi
035    __
$a (PubMed)33291419
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Zimmermann, Tomáš $u Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic
245    10
$a Large Scale Conversion of Trilobolide into the Payload of Mipsagargin: 8-O-(12-Aminododecanoyl)-8-O-Debutanoylthapsigargin / $c T. Zimmermann, P. Drašar, S. Rimpelová, SB. Christensen, VA. Khripach, M. Jurášek
520    9_
$a 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.
650    _2
$a fytogenní protinádorové látky $x chemie $x izolace a purifikace $7 D000972
650    _2
$a Apiaceae $x chemie $x metabolismus $7 D019661
650    _2
$a butyráty $x chemie $x izolace a purifikace $7 D002087
650    _2
$a oxid uhličitý $x chemie $7 D002245
650    12
$a techniky syntetické chemie $7 D060326
650    _2
$a superkritická fluidní chromatografie $x metody $7 D025924
650    _2
$a ovoce $x chemie $x metabolismus $7 D005638
650    _2
$a furany $x chemie $x izolace a purifikace $7 D005663
650    _2
$a lidé $7 D006801
650    _2
$a molekulární struktura $7 D015394
650    _2
$a nádory $x farmakoterapie $x patologie $7 D009369
650    _2
$a rostlinné extrakty $x chemie $7 D010936
650    _2
$a sarkoplazmatická Ca2+-ATPáza $x antagonisté a inhibitory $x metabolismus $7 D053498
650    _2
$a thapsigargin $x analogy a deriváty $x izolace a purifikace $7 D019284
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Drašar, Pavel $u Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic
700    1_
$a Rimpelová, Silvie $u Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic
700    1_
$a Christensen, Søren Brøgger $u Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 162, DK-2100 Copenhagen, Denmark
700    1_
$a Khripach, Vladimir A $u Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Kuprevich St. 5, 220141 Minsk, Belarus
700    1_
$a Jurášek, Michal $u Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic
773    0_
$w MED00188737 $t Biomolecules $x 2218-273X $g Roč. 10, č. 12 (2020)
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33291419 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210728 $b ABA008
991    __
$a 20210830101251 $b ABA008
999    __
$a ok $b bmc $g 1690483 $s 1140125
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 10 $c 12 $e 20201205 $i 2218-273X $m Biomolecules $n Biomolecules $x MED00188737
LZP    __
$a Pubmed-20210728

Find record

Citation metrics

Archiving options