Mini-review: discovery and development of platinum complexes designed to circumvent cisplatin resistance

Kèlland, Lloyd R.; Sharp, Swee Y.; O’Neill, Ciaran; Raynaud, Florence I.; Beale, Philip; Judson, Ian

doi:10.1016/s0162-0134(99)00141-5

Cited by 196 publications

(98 citation statements)

References 17 publications

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“…However, the lack of strong intermolecular NOE interactions is consistent with the proposed encapsulation model. From experiments with Q [6] and various aminoalkanes it was found that the protons further inside Q [6] exhibited the greatest upfield shift in the 1 H NMR spectra due to shielding effects. 56 Furthermore, protons that on average are located outside but near the portal exhibit slight downfield shifts.…”

Section: Encapsulation Of Di-ptmentioning

confidence: 99%

“…4 Much of the synthetic research over the last 20 years has focused on drugs that are able to overcome both resistance and the dose-limiting side-effects. [5][6][7][8][9] This has led to the approval of carboplatin and oxaliplatin for clinical use, 3 and the development of multinuclear platinum complexes. [10][11][12][13][14][15][16][17][18] Multinuclear platinum complexes are thought to overcome resistance through novel DNA binding modes.…”

Section: Introductionmentioning

confidence: 99%

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Cucurbit[n]uril binding of platinum anticancer complexes

et al. 2006

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The encapsulation of cisplatin by cucurbit [7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4 -dipyrazolylmethane (dpzm) ligand by Q [7] and cucurbit [8] 4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexes.

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Section: Encapsulation Of Di-ptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cucurbit[n]uril binding of platinum anticancer complexes

et al. 2006

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“…Thus, to circumvent resistance, alternative DNA damagesignaling pathways need to be evoked, as has been demonstrated experimentally with ionizing radiation and the platinum analog DACH-acetato-Pt Siddik et al, 1999). It is indeed likely that the demonstration of increased sensitivity of resistant cells to distinct platinum drugs, such as ZD0473 (Kelland et al, 1999) and oxaliplatin (Faivre et al, 1999) may in part reflect activation of independent pathways. Utilization of such agents in comparative investigations may prove to be invaluable for unraveling fully the mechanism of cisplatin resistance.…”

Section: Introductionmentioning

confidence: 99%

Cisplatin: mode of cytotoxic action and molecular basis of resistance

2003

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Cisplatin is one of the most potent antitumor agents known, displaying clinical activity against a wide variety of solid tumors. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of cisplatinbased chemotherapy. The mechanisms responsible for cisplatin resistance are several, and contribute to the multifactorial nature of the problem. Resistance mechanisms that limit the extent of DNA damage include reduced drug uptake, increased drug inactivation, and increased DNA adduct repair. Origins of these pharmacologicbased mechanisms, however, are at the molecular level. Mechanisms that inhibit propagation of the DNA damage signal to the apoptotic machinery include loss of damage recognition, overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3-K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and interference in caspase activation. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance.

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“…So, numerous derivatives of Pt(II)/ Pt(IV)-complexes have been prepared in recent years [4][5][6][7] . Since 2000, increased research on Platinum-complexes linked with polyamine ligands [8][9][10] . The amine groups of the polyamine linkers are groups capable of hydrogen bond formation with DNA atoms such as the O6 of guanine or the O3 of thymine 11 .…”

Section: Introductionmentioning

confidence: 99%

Nanospheres caped Pt(II) and Pt (IV): synthesis and evaluation as antimicrobial and Antifungal Agent

Öğütçü

Yetim

Özkan

et al. 2017

Polish Journal of Chemical Technology

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Antimicrobial and antifungal polymers are gaining the attention of pharmaceutical makers and industrial design. Nanospheres-Polymers attached Platinum(II) / (IV) complexes have been synthesized to investigate antimicrobial activities. Firstly, nanospheres involving Schiff bases were synthesized from (aminomethyl) polystyrene and four substitute salicylaldehyde (2-hydroxy benzaldehyde, 5-fl uoro-2-hydroxy benzaldehyde, 5-kloro-2-hydroxy benzaldehyde, 5-bromo-2-hydroxy benzaldehyde). Secondly, polymers attached Platinum(II) / (IV) complexes have been prepared by means of template method. The IR spectra show that the ligands act in a monovalent bidentate fashion all nanospheres involving Schiff bases. Square-planar and octahedral structures are proposed for Pt(II) and Pt(IV), respectively. All these substances have been examined for antibacterial activity against pathogenic strains, and antifungal activity. In particular, Pt(IV) complexes were more potent bactericides than all of the synthesized substances.

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Mini-review: discovery and development of platinum complexes designed to circumvent cisplatin resistance

Cited by 196 publications

References 17 publications

Cucurbit[n]uril binding of platinum anticancer complexes

Cucurbit[n]uril binding of platinum anticancer complexes

Cisplatin: mode of cytotoxic action and molecular basis of resistance

Nanospheres caped Pt(II) and Pt (IV): synthesis and evaluation as antimicrobial and Antifungal Agent

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