-
Something wrong with this record ?
Synthesis and Pharmacological Effects of Diosgenin-Betulinic Acid Conjugates
Z. Özdemir, M. Rybková, M. Vlk, D. Šaman, L. Rárová, Z. Wimmer
Language English Country Switzerland
Document type Journal Article
Grant support
FV10599
Ministerstvo Průmyslu a Obchodu
FV30300
Ministerstvo Průmyslu a Obchodu
NLK
Directory of Open Access Journals
from 1997
Free Medical Journals
from 1997
PubMed Central
from 2001
Europe PubMed Central
from 2001
ProQuest Central
from 1997-01-01
Open Access Digital Library
from 1997-01-01
Medline Complete (EBSCOhost)
from 2009-03-01
Health & Medicine (ProQuest)
from 1997-01-01
- MeSH
- Cycloaddition Reaction MeSH
- Diosgenin chemistry MeSH
- Hydrogenation MeSH
- Catalysis MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Palladium chemistry MeSH
- Pentacyclic Triterpenes chemistry MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Pressure MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The target diosgenin-betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc21012290
- 003
- CZ-PrNML
- 005
- 20210507103709.0
- 007
- ta
- 008
- 210420s2020 sz f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.3390/molecules25153546 $2 doi
- 035 __
- $a (PubMed)32756514
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a sz
- 100 1_
- $a Özdemir, Zülal $u Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic $u Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technická 5, 16628 Prague 6, Czech Republic
- 245 10
- $a Synthesis and Pharmacological Effects of Diosgenin-Betulinic Acid Conjugates / $c Z. Özdemir, M. Rybková, M. Vlk, D. Šaman, L. Rárová, Z. Wimmer
- 520 9_
- $a The target diosgenin-betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 ± 1.1 µM), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.
- 650 _2
- $a protinádorové látky $x chemická syntéza $x chemie $x farmakologie $7 D000970
- 650 _2
- $a katalýza $7 D002384
- 650 _2
- $a nádorové buněčné linie $7 D045744
- 650 _2
- $a viabilita buněk $x účinky léků $7 D002470
- 650 _2
- $a cykloadiční reakce $7 D061565
- 650 _2
- $a diosgenin $x chemie $7 D004144
- 650 _2
- $a screeningové testy protinádorových léčiv $7 D004354
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a hydrogenace $7 D006865
- 650 _2
- $a palladium $x chemie $7 D010165
- 650 _2
- $a pentacyklické triterpeny $x chemie $7 D053978
- 650 _2
- $a tlak $7 D011312
- 650 _2
- $a vztahy mezi strukturou a aktivitou $7 D013329
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Rybková, Michaela $u Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technická 5, 16628 Prague 6, Czech Republic
- 700 1_
- $a Vlk, Martin $u Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic $u Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, Břehová 7, 11519 Prague 1, Czech Republic
- 700 1_
- $a Šaman, David $u Department of NMR Spectroscopy, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 2, 16610 Prague 6, Czech Republic
- 700 1_
- $a Rárová, Lucie $u Laboratory of Growth Regulators, Faculty of Science, Palacký University, and Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, 78371 Olomouc, Czech Republic
- 700 1_
- $a Wimmer, Zdeněk $u Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic $u Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technická 5, 16628 Prague 6, Czech Republic
- 773 0_
- $w MED00180394 $t Molecules (Basel, Switzerland) $x 1420-3049 $g Roč. 25, č. 15 (2020)
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/32756514 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20210420 $b ABA008
- 991 __
- $a 20210507103707 $b ABA008
- 999 __
- $a ok $b bmc $g 1650620 $s 1132669
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2020 $b 25 $c 15 $e 20200803 $i 1420-3049 $m Molecules $n Molecules $x MED00180394
- GRA __
- $a FV10599 $p Ministerstvo Průmyslu a Obchodu
- GRA __
- $a FV30300 $p Ministerstvo Průmyslu a Obchodu
- LZP __
- $a Pubmed-20210420