Novel oxaliplatin(<scp>iv</scp>) complexes conjugated with ligands bearing pendant 1,2-dithiolane/1,2-diselenolane/cyclopentyl motifs

Liu, Xiao; Wenisch, Dominik; Barth, Marie‐Christin; Cseh, Klaudia; Kowol, Christian R.; Jakupec, Michael A.; Gibson, Dan; Keppler, Bernhard K.; Weigand, Wolfgang

doi:10.1039/d2dt02217f

Cited by 6 publications

(3 citation statements)

References 65 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We routinely synthesize Ent-β-lactams from l -Ent-PEG 3 -N 3 6 and alkyne-modified β-lactams using Cu(II) and sodium ascorbate (NaAsc) to generate Cu(I) in situ . ,, Although this approach affords Ent-β-lactams in moderate to high yields (40–80%), , we did not employ it in the synthesis of l / d -EP due to the concern of potential Pt(IV) reduction caused by NaAsc. ,− During attempts to optimize the CuAAC reaction described above that afforded l / d -EOP 3,4 , we reconsidered in situ reduction of Cu(II) and evaluated the stability of oxPt(IV)-alkyne 5 in the presence of NaAsc in water and DMF. We found that oxPt(IV)-alkyne 5 remained stable throughout the 8 h incubation with NaAsc.…”

Section: Resultsmentioning

confidence: 99%

Investigation of Siderophore–Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo

Guo,

Wang,

Nolan

2024

ACS Infect. Dis.

View full text Add to dashboard Cite

The growing threat of bacterial infections coupled with the dwindling arsenal of effective antibiotics has heightened the urgency for innovative strategies to combat bacterial pathogens, particularly Gram-negative strains, which pose a significant challenge due to their outer membrane permeability barrier. In this study, we repurpose clinically approved anticancer agents as targeted antibacterials. We report two new siderophore−platinum-(IV) conjugates, both of which consist of an oxaliplatin-based Pt(IV) prodrug (oxPt(IV)) conjugated to enterobactin (Ent), a triscatecholate siderophore employed by Enterobacteriaceae for iron acquisition. We demonstrate that L/D-Ent-oxPt(IV) (L/D-EOP) are selectively delivered into the Escherichia coli cytoplasm, achieving targeted antibacterial activity, causing filamentous morphology, and leading to enhanced Pt uptake by bacterial cells but reduced Pt uptake by human cells. D-EOP exhibits enhanced potency compared to oxaliplatin and L-EOP, primarily attributed to the intrinsic antibacterial activity of its non-native siderophore moiety. To further elucidate the antibacterial activity of Ent−Pt(IV) conjugates, we probed DNA damage caused by L/D-EOP and the previously reported cisplatin-based conjugates L/D-Ent-Pt(IV) (L/ D-EP). A comparative analysis of these four conjugates reveals a correlation between antibacterial activity and the ability to induce DNA damage. This work expands the scope of Pt cargos targeted to the cytoplasm of Gram-negative bacteria via Ent conjugation, provides insight into the cellular consequences of Ent−Pt(IV) conjugates in E. coli, and furthers our understanding of the potential of Pt-based therapeutics for antibacterial applications.

show abstract

Section: Resultsmentioning

confidence: 99%

Investigation of Siderophore–Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo

Guo,

Wang,

Nolan

2024

ACS Infect. Dis.

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that increased lipophilicity within homologous series of Pt(IV) complexes may lead to enhanced cellular accumulation via passive diffusion [47]. Generally, conjugation with hydrophobic ligands leads to enhanced lipophilicity.…”

Section: Cellular Accumulationmentioning

confidence: 99%

Multi-Action Platinum(IV) Prodrugs Conjugated with COX-Inhibiting NSAIDs

Liu

Wenisch

Dahlke

et al. 2023

Preprint

View full text Add to dashboard Cite

“…6 Therefore, the reduction of Pt(IV) is a relevant process since the prodrug will be inactive if it is not easily reduced inside the cell and, on the other hand, if the reduction occurs before uptake into the cell, severe side effects will occur. 7 However, the rates of reduction depend on the ability of the ligands coordinated to Pt(IV) to facilitate the electron transfer from the reducing agent so that they do not necessarily correlate with the reduction potentials. 8,9 Several Pt(IV) compounds such as iproplatin, satraplatin, and tetraplatin, shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

Exploring the effect of the axial ligands on the anticancer activity of [C,N,N′] Pt(iv) cyclometallated compounds

Lázaro,

Bosque,

Marín

et al. 2024

Dalton Trans.

View full text Add to dashboard Cite

show abstract

Novel oxaliplatin(iv) complexes conjugated with ligands bearing pendant 1,2-dithiolane/1,2-diselenolane/cyclopentyl motifs

Abstract: In this work, multiple biologically active α-lipoic acid (ALA) and its isologous 1,2-diselenolane (SeA) and cyclopentyl (CpA) analogues were investigated for their differences in redox potentials, cytotoxicity and ROS production....

Cited by 6 publications

References 65 publications

Investigation of Siderophore–Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo

Investigation of Siderophore–Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo

Multi-Action Platinum(IV) Prodrugs Conjugated with COX-Inhibiting NSAIDs

Exploring the effect of the axial ligands on the anticancer activity of [C,N,N′] Pt(iv) cyclometallated compounds

Contact Info

Product

Resources

About