Sulfide and phosphine ligands in carboplatin analogs

Sampedro, F.; Molins-Pujol, A.M.; Bonal, J.; Barbé, Jordi; Garrido, Salvador; Pueyo, M; Llagostera, Montserrat; Sánchez‐Ferrando, Francisco

doi:10.1016/0223-5234(91)90150-l

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…Ligand structural compositions beyond am(m)ines, specifically Pt-phosphine or mixed phosphine/am(m)ine complexes, also show considerable antitumor activity. − Complexes with open or exchangeable coordination positions appear to operate in the more classic cisplain-like manner via DNA adduct formation, ,,,,,− while coordinatively saturated structures, especially those with chelating lipophilic phosphines, are proposed to function by a unique anti-mitochondrial mechanism. ,, This functional divergence may be the reason that these cationic complexes are active against cisplatin-resistant cells.…”

Section: Introductionmentioning

confidence: 99%

Utilizing Redox-Mediated Bergman Cyclization toward the Development of Dual-Action Metalloenediyne Therapeutics

et al. 2013

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Reaction of 2 equiv of 1,2-bis((diphenylphosphino)ethynyl)benzene (dppeb, 1) with Pt(cod)Cl2 followed by treatment with N2H4 yields the reduced Pt(0) metalloenediyne, Pt(dppeb)2, 2. This complex is stable to both air oxidation and metal-mediated Bergman cyclization under ambient conditions due to the nearly idealized tetrahedral geometry. Reaction of 2 with 1 equiv of I2 in the presence of excess 1,4-cyclohexadiene (1,4-CHD) radical trap rapidly and near-quantitatively generates the cis-Bergman-cyclized, diiodo product 3 ((31)P: δ = 41 ppm, J(Pt-P) = 3346 Hz) with concomitant loss of 1 equiv of uncyclized phosphine chelate ((31)P: δ = -33 ppm). In contrast, addition of 2 equiv of I2 in the absence of additional radical trap instantaneously forms a metastable Pt(dppeb)2(2+) intermediate species, 4, that is characterized by δ = 51 ppm in the (31)P NMR (J(Pt-P) = 3171 Hz) and ν(C≡C) = 2169 cm(-1) in the Raman profile, indicating that it is an uncyclized, bis-ligated complex. Over 24 h, 4 undergoes ligand exchange to form a neutral, square planar complex that spontaneously Bergman cyclizes at ambient temperature to give the crystalline product Pt(dppnap-I2)I2 (dppnap-I2 = (1,4-diiodonaphthalene-2,3-diyl)bis(diphenylphosphine)), 5, in 52% isolated yield. Computational analysis of the oxidation reaction proposes two plausible flattened tetrahedral structures for intermediate 4: one where the phosphine core has migrated to a trans-spanning chelate geometry, and a second, higher energy structure (3.3 kcal/mol) with two cis-chelating phosphine ligands (41° dihedral angle) via a restricted alkyne-terminal starting point. While the energies are disparate, the common theme in both structures is the elongated Pt-P bond lengths (>2.4 Å), indicating that nucleophilic ligand substitution by I(-) is on the reaction trajectory to the cyclized product 5. The efficiency of the redox-mediated Bergman cyclization reaction of this stable Pt(0) metalloenediyne prodrug and resulting cisplatin-like byproduct represents an intriguing new strategy for potential dual-threat metalloenediyne therapeutics.

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Section: Introductionmentioning

confidence: 99%

Utilizing Redox-Mediated Bergman Cyclization toward the Development of Dual-Action Metalloenediyne Therapeutics

et al. 2013

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“…It can detect mutagens at a much lower concentration than the E. coli and Salmonella mutation assays, owing to the high permeability of chemicals through the cell membrane of B. subtilis (Yamaguchi, 1989). Cisplatin (Sampedro et al, 1991;Khokhar et al, 1993), which is widely used as a cancer chemotherapeutic drug causing DNA damage, was chosen as a standard drug for comparing the activity with the tested compounds.…”

Section: Resultsmentioning

confidence: 99%

A study on the genotoxic activities of some new benzoxazoles

et al. 2007

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The Bacillus subtilis rec assay has been specially developed to detect DNA-damaging potential in chemicals, with the rationale based on the relative difference of survival of a DNA repair combination proficient strains and its deficient strain, which is interpreted as genotoxicity. The genotoxic activities of newly (1-6) and previously (7-18) synthesized various benzoxazoles and benzimidazoles were analyzed via the B. subtilis rec assay. Newly obtained benzoxazole and benzimidazole derivatives (1-6) were synthesized in the presence of polyphosphoric acid (PPA) and 6 N HCl, respectively to detect their DNA-damaging activities. Among the tested compounds, 6-methyl-2-(o-chlorophenyl)benzoxazole (9), 5-amino-2-(p-methylbenzyl)benzoxazole (4), 5-(p-fluorobenzamido)-2-phenylbenzoxazole (13), and 2-(p-methylaminophenyl)benzoxazole (18) showed genotoxic activities having Rec 50 values of 1.85, 1.74, 1.60, and 1.50 or S-probit values of 0.534, 0.482, 0.460, and 0.357, respectively. On the other hand, 2-(p-bromobenzyl)-5-methylbenzimidazole (6) and 2-benzyl-5-(p-fluorophenylacetamido)-benzoxazole (15) were exhibited a reverse effect that displayed a bacterial growth in the recstrains while there was no any bacterial growth in rec + strains at the same concentration.

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“…It has been supposed that the distribution and the concentration of platinum-based drugs in different body districts are influenced by physicochemical properties of the ligands such as polarity, hydrophilicity, and steric requirements [3]. Among several other modifications, the possibility of structurally modifying cisplatin by introducing phosphines as neutral ligands has been considered [4,5].…”

Section: Introductionmentioning

confidence: 99%

Nafion®-Containing Solid Lipid Nanoparticles as a Tool for Anticancer Pt Delivery: Preliminary Studies

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Drechsler

et al. 2017

Journal of Chemistry

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Preliminary studies of nanoparticles based on the perfluorosulfonic acid resin Nafion have been carried out with the aim of establishing an ionic connection with the protonable phosphine 1,3,5-triaza-7-phosphaadamantane (PTA), suitable for the coordination of platinum. Nafion-containing nanoparticles (NAF) were produced by homogenization followed by ultrasonication method. After production, NAF were characterized in terms of size, morphology, and in vitro cytotoxicity. The PCS studies showed that the -average mean diameter was around 250 nm. Moreover, the polydispersity index showed a monodimensional distribution of nanoparticles. Cryo-TEM analysis showed a uniform and homogenous population of particles, characterized by the presence of both ovoidal and needle-like structures. To evaluate the in vitro cytotoxicity, NAF were tested on human cancer cell lines K562 and A2780. No cytotoxic effect was found on both cell lines. By 13 P-NMR measures, it is here proved that the strongly acidic sulfonic groups of Nafion-containing nanoparticles (NAF) can act as protonating agents for PTA. The protonation occurs selectively at nitrogen; hence protonated PTA maintains its ability to coordinate platinum via its phosphorus atom.

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Sulfide and phosphine ligands in carboplatin analogs

Cited by 6 publications

References 9 publications

Utilizing Redox-Mediated Bergman Cyclization toward the Development of Dual-Action Metalloenediyne Therapeutics

Utilizing Redox-Mediated Bergman Cyclization toward the Development of Dual-Action Metalloenediyne Therapeutics

A study on the genotoxic activities of some new benzoxazoles

Nafion®-Containing Solid Lipid Nanoparticles as a Tool for Anticancer Pt Delivery: Preliminary Studies

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