New glycoconjugation strategies for Ruthenium(II) arene complexes via phosphane ligands and assessment of their antiproliferative activity

Iacopini, Dalila; Vančo, Ján; Pietro, Sebastiano Di; Bordoni, Vittorio; Zacchini, Stefano; Marchetti, Fabio; Dvořák, Zdeněk; Malina, Tomáš; Biancalana, Lorenzo; Trávnı́ček, Zdeněk; Bussolo, Valeria Di

doi:10.1016/j.bioorg.2022.105901

Cited by 9 publications

(11 citation statements)

References 79 publications

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“…Importantly, complex Os-7 had the same IC 50 value on both cell lines. Structurally unrelated Ru(II) and Os(II) complexes ( Hildebrandt et al, 2022 ; Iacopini et al, 2022 ) can overcome cisplatin resistance in A2780 and SKOV3 cell models, similarly to our compounds.…”

Section: Discussionmentioning

confidence: 69%

“…Selectivity was assessed for structurally unrelated Os(II) and Ru(II) complexes with cinnamic acid-derived ligands that were selective for ovarian cancer cells and had no impact on the proliferation of keratinocytes, fibroblasts (Hildebrandt et al, 2022). Selectivity is not a common feature of Ru(II) or Os(II) complexes, as in another study (Iacopini et al, 2022) glycoconjugated ruthenium(II) arene complexes had no selectivity for non-transformed cells.…”

Section: Discussionmentioning

confidence: 99%

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Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria

et al. 2023

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The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis. We exchanged the benzoyl protective groups to straight chain alkanoyl groups with varying length (3 to 7 carbon units) that increased the IC50 value as compared to the benzoyl-protected complexes and rendered the complexes toxic. These results suggest a need for aromatic groups in the molecule. The pyridine moiety of the bidentate ligand was exchanged for a quinoline group to enlarge the apolar surface of the molecule. This modification decreased the IC50 value of the complexes. The complexes containing [(η6-p-cymene)Ru(II)], [(η6-p-cymene)Os(II)] or [(η5-Cp*)Ir(III)] were biologically active unlike the complex containing [(η5-Cp*)Rh(III)]. The complexes with cytostatic activity were active on ovarian cancer (A2780, ID8), pancreatic adenocarcinoma (Capan2), sarcoma (Saos) and lymphoma cell lines (L428), but not on primary dermal fibroblasts and their activity was dependent on reactive oxygen species production. Importantly, these complexes were cytostatic on cisplatin-resistant A2780 ovarian cancer cells with similar IC50 values as on cisplatin-sensitive A2780 cells. In addition, the quinoline-containing Ru and Os complexes and the short chain alkanoyl-modified complexes (C3 and C4) proved to be bacteriostatic in multiresistant Gram-positive Enterococcus and Staphylococcus aureus isolates. Hereby, we identified a set of complexes with submicromolar to low micromolar inhibitory constants against a wide range of cancer cells, including platinum resistant cells and against multiresistant Gram-positive bacteria.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria

et al. 2023

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“…Aliphatic polyketones made of ethylene, propylene, and carbon monoxide were synthesized according to a reported procedure yielding a polyketone with 30 mol% ethylene and 70 mol% propylene (PK) ( M w 2930). 21 DPS12 was synthesized as previously reported, 22 whereas DPS11 (ref. 23 ) was prepared by means of an unprecedented synthetic pathway, as described below ( Fig.…”

Section: Methodsmentioning

confidence: 99%

Functionalized aliphatic polyketones with germicide activity

et al. 2022

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“…Carbohydrate ligands incorporated into an organometallic moiety have several advantages compared with simple organic ligands, 17 (see Figure 1 for selected examples 1 – 6 ). For example, cancer cells have higher uptake of glucose and some other monosaccharides (phenomenon known as the Warburg effect 26 ) due to their aberrant metabolism, 26 and glucose modified in a specific position (even with a sterically demanding organometallic moiety) can retain its affinity to glucose transporters overexpressed in cancer tissues leading to higher activity or selectivity, as was demonstrated for glucose analogs carrying platinum complexes at the 6‐position, 27 or the analog 1 with a ruthenium complex at the same position 18 .…”

Section: Introductionmentioning

confidence: 99%

Improving the anticancer activity of fluorinated glucosamine and galactosamine analogs by attachment of a ferrocene or ruthenium tetrazene motif

Hamala,

Ondrášková,

Červenková Šťastná

et al. 2024

Applied Organom Chemis

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Acylated N‐acetyl hexosamine hemiacetals are known for their cytotoxicity. We have previously reported that cytotoxicity can be increased by replacing one or more acyloxy groups with fluorine. Herein, we present the synthesis of 4,6‐difluorinated d‐gluco‐ and 4‐fluorinated d‐galacto‐configured hexosamine‐derived glycoconjugates with organoruthenium or ferrocene complexes and their in vitro cytotoxicity against three cancer cell lines (A2780, SK‐OV‐3, and MDA‐MB‐231) and one noncancerous cell line (HEK‐293). The attachment of the organometallic moiety at the 2‐position significantly enhanced the cytotoxicity, especially against triple‐negative MDA‐MB‐231 and the cisplatin resistant SK‐OV‐3 cancer cells. We observed a clear significance of an unprotected and acetyl protected anomeric hydroxyl for the cytotoxicity. Glycoconjugates with a non‐hydrolysable organic or organometallic group at the anomeric position were generally nontoxic. A more detailed analysis revealed that, in particular, complexes with the ruthenium tetrazene complex induced apoptosis in both SK‐OV‐3 and MDA‐MB‐231 cells, as demonstrated by western blot analysis and Annexin V‐FITC/PI staining. The structures of the two most cytotoxic organoruthenium and ferrocene glycoconjugates were confirmed by X‐ray diffraction analysis.

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New glycoconjugation strategies for Ruthenium(II) arene complexes via phosphane ligands and assessment of their antiproliferative activity

Cited by 9 publications

References 79 publications

Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria

Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria

Functionalized aliphatic polyketones with germicide activity

Improving the anticancer activity of fluorinated glucosamine and galactosamine analogs by attachment of a ferrocene or ruthenium tetrazene motif

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