New glycoconjugation strategies for Ruthenium(II) arene complexes via phosphane ligands and assessment of their antiproliferative activity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F22%3A73617076" target="_blank" >RIV/61989592:15640/22:73617076 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0045206822003066?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206822003066?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bioorg.2022.105901" target="_blank" >10.1016/j.bioorg.2022.105901</a>
Alternative languages
Result language
angličtina
Original language name
New glycoconjugation strategies for Ruthenium(II) arene complexes via phosphane ligands and assessment of their antiproliferative activity
Original language description
Glycoconjugation is a powerful tool to improve the anticancer activity of metal complexes. Herein, we modified commercial arylphosphanes with carbohydrate-derived fragments for the preparation of novel glycoconjugated ruthenium(II) p-cymene complexes. Specifically, D-galactal and D-allal-derived vinyl epoxides (VE beta and VE alpha) were coupled with (2-hydroxyphenyl)diphenylphosphane, affording the 2,3-unsaturated glycophosphanes 1 beta and 1 alpha. Ligand exchange with [Ru(C2O4)(eta(6)-p-cymene)(H2O)] gave the glycoconjugated complexes Ru1 beta and Ru1 alpha which were subsequently dihydroxylated with OsO4/N-methylmorpholine N-oxide to Ru2 beta and Ru2 alpha containing O-benzyl D-mannose and D-gulose units respectively. Besides, aminoethyl tetra-O-acetyl-beta-D-gluco-pyranoside was condensed with borane-protected (4-diphenylphosphanyl)benzoic acid by HATU/DIPEA under MW heating, to afford the amide 3 center dot BH3. Zemplen deacylation with MeONa/MeOH gave the deprotected D-glucopyranoside derivative 4 center dot BH3. The glycoconjugated phosphane complexes Ru3 and Ru4 were obtained by reaction of the phosphane-boranes 3 center dot BH3 and 4 center dot BH3 with [Ru(C2O4)(eta(6)-p-cymene)(H2O)]. The employed synthetic strategies were devised to circumvent unwanted phosphine oxidation. The compounds were purified by silica chromatography, isolated in high yield and purity and characterized by analytical and spectroscopic (IR and multinuclear NMR) techniques. The behaviour of the six glycoconjugated Ru complexes in aqueous solutions was assessed by NMR and MS measurements. All compounds were screened for their in vitro cytotoxicity against A2780/A2780R human ovarian and MCF7 breast cancer cell lines, revealing a significant cytotoxicity for complexes containing the 2,3-unsaturated glycosyl unit (Ru1 beta, Ru1 alpha). Additional studies on five other human cancer cells, as well as time-dependent toxicity and cell-uptake analyses on ovarian cancer cells, confirmed the prominent activity of these two compounds - higher than cisplatin - and the better performance of the beta anomer. However, Ru1 beta, Ru1 alpha did not show preferential activity against cancer cells with respect to fetal lung fibroblast and human embryonic kidney cells as models of normal cells. The effects of the two ruthenium glycoconjugated compounds in A2780 ovarian cancer cells were further investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The latter is a relevant factor in the mechanism of action of the highly cytotoxic Ru1 beta, inducing cell death by apoptosis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10402 - Inorganic and nuclear chemistry
Result continuities
Project
<a href="/en/project/EF16_019%2F0000754" target="_blank" >EF16_019/0000754: Nanotechnologies for Future</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
BIOORGANIC CHEMISTRY
ISSN
0045-2068
e-ISSN
1090-2120
Volume of the periodical
126
Issue of the periodical within the volume
September
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
nestrankovano
UT code for WoS article
000833463700003
EID of the result in the Scopus database
2-s2.0-85131454851