Porphyrin platinum conjugates – new aims

Brunner, Henri; Arndt, Marion; Treittinger, B.

doi:10.1016/s0020-1693(03)00479-1

Cited by 34 publications

(21 citation statements)

References 41 publications

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“…16 This similarity in activity is encouraging considering the many known platinum conjugates with reduced activity. 17,18 MMPt, 19 a Pt complex similar to that present in conjugate 1 , provided similar antiproliferative activity relative to both 1 and carboplatin. Cisplatin displayed the greatest cytotoxicity towards this cell line with an IC 50 of 0.31 ± 0.06 μ M. 20 …”

mentioning

confidence: 85%

Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin–platinum conjugate

Arambula

Sessler

Siddik

2011

Bioorganic & Medicinal Chemistry Letters

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In our effort to investigate further texaphyrin conjugation as a means of increasing delivery and accumulation of known anticancer platinum agents in cancer cells, we have continued our studies on the mode of action of a texaphyrin-platinum conjugate, particularly in cisplatin-resistant tumor cells that are characterized by several mechanisms of resistance, including reduced drug accumulation. Our results provide support for the proposal that intracellular platinum and Pt-DNA adduct levels were significantly increased using our conjugate relative to corresponding Pt controls. Moreover, no differences were found in cellular accumulation and Pt-DNA adduct formation between Pt sensitive and Pt resistant ovarian cells. As a result, resistance to the conjugate was lower than cisplatin in resistant cells. Based on these results we conclude that texaphyrin conjugation provides a promising strategy for overcoming biochemical pharmacologic mechanisms of resistance.

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mentioning

confidence: 85%

Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin–platinum conjugate

Arambula

Sessler

Siddik

2011

Bioorganic & Medicinal Chemistry Letters

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“…Conjugate 7 displayed a similar level of activity (IC 50 = 1.4 µM) as carboplatin within error. This similarity in actvity is encouraging considering the many known platinum conjugates with reduced activity 36,48. While it may be inferred from the similarity in IC 50 values between carboplatin and conjugate 7 that activity may be attributed to platinum delivery, this has yet to be shown experimentally.…”

Section: Resultsmentioning

confidence: 70%

Gadolinium texaphyrin (Gd-Tex)-malonato-platinum conjugates: Synthesis and comparison with carboplatin in normal and Pt-resistant cell lines

et al. 2009

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The synthesis of a new PEG 3 -solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH 3 ) 2 moiety is described. The effect of the tumor localizing Gd-Tex macrocycle on platinum activity was evaluated in cell culture. The malonate moiety, analogous to that present in carboplatin, is expected to release Pt(NH 3 ) 2 under physiological conditions. The half-life in phosphate-buffered saline was found to be ca. 3 days at room temperature, and the hydrolytic product released from the conjugate was collected and confirmed as Pt-based by flameless atomic absorption spectrophotometry. Anti-proliferative activity was tested using A549 human lung cancer and A2780 human ovarian cancer cell lines. In both cell lines, the activity of the Gd-Tex conjugate was found to be similar to that of carboplatin. Efficacy against a Pt-resistant ovarian cell line greater than that displayed by carboplatin was also observed.

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“…Although the exact mechanism for photodynamic therapy of porphyrins in abnormal tissues is still not well known, numerous studies have confirmed its efficacy to be depend on the environmental characteristics and physicochemical properties of photosensitizer [6][7][8][9]. The free base TPPS (H 2 tpps 4-), Figure 1, can be protonated by one or two protons on pyrrolinic nitrogen's resulting to the mono (H 3 tpps 3-) and di-protonated (H 4 tpps 2-) species which have drastically different physicochemical properties such as aggregation and lipophilicity which lead to different cellular uptake and photodynamic effect [10,11]. As shown in some studies, protonation of photosensitizer compounds leads to higher cellular uptake [6,7].…”

Section: Introductionmentioning

confidence: 99%

Solvent effect on protonation of tpps in water-DMF mixtures

Farajtabar¹,

Faeli²

2017

Bull. Chem. Soc. Eth.

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ABSTRACT. The protonation of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin was investigated in aqueous solutions of N,N-dimethyformamide at 25 C and 0.1 mol.dm -3 sodium perchlorate. The solvent effect on value of protonation constant was examined by using the linear solvation energy relationship concept. The value of logK1, logK2 and logKt was correlated with the macroscopic (dielectric constant) and microscopic Kamlet-Taft parameters (,  and *) of binary mixtures. The solvent effects were analyzed in the terms of Kamlet, Abboud and Taft model (KAT). Multiple linear regression were used to find the contribution of the microscopic parameters containing  (hydrogen-bond acidity), * (dipolarity/polarizability) and  (hydrogen-bond basicity). It was found that  and  were the most predominant descriptors. Also, relationship with reciprocal of dielectric constant was obtained based on Born's model, showing the significance of specific solute-solvent interactions. Therefore the hydrogen bonding interactions between solute and solvent components are mainly responsible for the change in protonation constants of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin in water-N,N-dimethyformamid binary mixtures.

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Porphyrin platinum conjugates – new aims

Cited by 34 publications

References 41 publications

Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin–platinum conjugate

Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin–platinum conjugate

Gadolinium texaphyrin (Gd-Tex)-malonato-platinum conjugates: Synthesis and comparison with carboplatin in normal and Pt-resistant cell lines

Solvent effect on protonation of tpps in water-DMF mixtures

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