Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 11868-11876 |
| Number of pages | 9 |
| Journal | Chem. Eur. J. |
| Volume | 26 |
| Issue number | 51 |
| DOIs | |
| Publication status | Published - 2020 |
Keywords
- allylation
- N-trifluoromethyl N-heterocyclic carbenes
- organoids
- ovarian cancer
- palladium allyl complexes
- Diseases
- Organometallics
- Synthesis (chemical)
- Anti-cancer agents
- Anti-tumor activities
- Antiproliferative agents
- Mechanism of action
- N-heterocyclic carbenes
- Nucleophilic attack
- Organometallic compounds
- Palladium complexes
- Palladium compounds
- antineoplastic agent
- cisplatin
- coordination compound
- ligand
- palladium
- cell proliferation
- chemistry
- drug effect
- female
- human
- ovary tumor
- pathology
- tumor cell line
- Antineoplastic Agents
- Cell Line, Tumor
- Cell Proliferation
- Cisplatin
- Coordination Complexes
- Female
- Humans
- Ligands
- Ovarian Neoplasms
- Palladium
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Palladium(II)-η3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids : Chemistry - A European Journal. / Scattolin, T.; Bortolamiol, E.; Visentin, F.; Palazzolo, S.; Caligiuri, I.; Perin, T.; Canzonieri, V.; Demitri, N.; Rizzolio, F.; Togni, A.
In: Chem. Eur. J., Vol. 26, No. 51, 2020, p. 11868-11876.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Palladium(II)-η3-Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids
T2 - Chemistry - A European Journal
AU - Scattolin, T.
AU - Bortolamiol, E.
AU - Visentin, F.
AU - Palazzolo, S.
AU - Caligiuri, I.
AU - Perin, T.
AU - Canzonieri, V.
AU - Demitri, N.
AU - Rizzolio, F.
AU - Togni, A.
N1 - Cited By :6 Export Date: 18 February 2021 CODEN: CEUJE Correspondence Address: Scattolin, T.; Department of Chemistry and Centre for Sustainable Chemistry, Krijgslaan 281,S-3, Belgium; email: thomas.scattolin@ugent.be Correspondence Address: Visentin, F.; Department of Molecular Sciences and Nanosystems, Campus Scientifico Via Torino 155, Italy; email: fvise@unive.it Correspondence Address: Togni, A.; Department of Chemistry and Applied Biosciences, Vladimir-Prelog-Weg 2, Switzerland; email: antonio.togni@inorg.chem.ethz.ch Chemicals/CAS: cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; Antineoplastic Agents; Cisplatin; Coordination Complexes; Ligands; Palladium Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC, AIRC IG23566 Funding text 1: F.R. was financially supported by the Fondazione AIRC per la Ricerca sul Cancro (grant AIRC IG23566) and V.C. by the Ministero della Salute—Ricerca Corrente. 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PY - 2020
Y1 - 2020
N2 - The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η3-allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02–0.5 μm). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3-allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids. © 2020 Wiley-VCH GmbH
AB - The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η3-allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02–0.5 μm). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3-allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids. © 2020 Wiley-VCH GmbH
KW - allylation
KW - N-trifluoromethyl N-heterocyclic carbenes
KW - organoids
KW - ovarian cancer
KW - palladium allyl complexes
KW - Diseases
KW - Organometallics
KW - Synthesis (chemical)
KW - Anti-cancer agents
KW - Anti-tumor activities
KW - Antiproliferative agents
KW - Mechanism of action
KW - N-heterocyclic carbenes
KW - Nucleophilic attack
KW - Organometallic compounds
KW - Palladium complexes
KW - Palladium compounds
KW - antineoplastic agent
KW - cisplatin
KW - coordination compound
KW - ligand
KW - palladium
KW - cell proliferation
KW - chemistry
KW - drug effect
KW - female
KW - human
KW - ovary tumor
KW - pathology
KW - tumor cell line
KW - Antineoplastic Agents
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Cisplatin
KW - Coordination Complexes
KW - Female
KW - Humans
KW - Ligands
KW - Ovarian Neoplasms
KW - Palladium
U2 - 10.1002/chem.202002199
DO - 10.1002/chem.202002199
M3 - Article
VL - 26
SP - 11868
EP - 11876
JO - Chem. Eur. J.
JF - Chem. Eur. J.
SN - 0947-6539
IS - 51
ER -