Synthesis and antitumor activity of ammine/amine platinum(II) and (IV) complexes

Khokhar, Abdul R.; Deng, Yuanjian; Al-Baker, Salaam; Yoshida, Motofumi; Siddik, Zahid H.

doi:10.1016/0162-0134(93)85039-b

Cited by 51 publications

(24 citation statements)

References 12 publications

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“…9, 47 The fact that these complexes do indeed exhibit cytotoxicity confirms that they are meaningful models of active anticancer complexes. If, for example, a much lower cytotoxicity was observed, any subsequent conclusions about the cellular location of the complex would be less applicable to other complexes with known anticancer activity.…”

Section: Cytotoxicitymentioning

confidence: 73%

Investigations using fluorescent ligands to monitor platinum(iv) reduction and platinum(ii) reactions in cancer cells

et al. 2009

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Coordination of the aniline containing fluorophores, coumarin 120 (C120) and coumarin 151 (C151) at the non-leaving group positions of cisplatin analogues (giving cis-[PtCl(2)(C120)(NH(3))] and cis-[PtCl(2)(C151)(NH(3))]) resulted in partial and complete quenching of the fluorescence, respectively. Oxidation of the coumarin 120 complex to the Pt(iv) form (cis,trans,cis-[PtCl(2)(OH)(2)(C120)(NH(3))]) resulted in further quenching compared to that seen for the Pt(ii) complex. The fluorescence profiles of these coumarin complexes were collected to evaluate their suitability for studying the metabolism of cisplatin-based anticancer drugs. C151 has the more suitable profile with a lower energy excitation peak and a better separation between the excitation and emission spectra. The complete damping of fluorescence on coordination to Pt(ii) makes it unsuitable for monitoring the reduction process, but does allow it to be used to monitor loss of the aniline type ligand. All of the coumarin complexes revealed moderate cyotoxcities in the range 10-22 microM indicating that they are suitable models of anticancer agents. DNA dampens the fluorescence of both Pt(ii) complexes and that of C120 has a much higher DNA binding affinity (10 000 M(-1)) than does the complex of C151 (300 M(-1)). Treatment of A2780 human ovarian carcinoma cells with the Pt-coumarin complexes resulted in fluorescence visible by confocal microscopy, and co-localisation studies with organelle specific dyes suggest they are concentrated in the late endosomes or lysosomes. Cells treated with the Pt(iv) complex of C120 revealed strong fluorescence and a somewhat different distribution to cells treated with the Pt(ii) complex indicating reduction following uptake.

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Section: Cytotoxicitymentioning

confidence: 73%

Investigations using fluorescent ligands to monitor platinum(iv) reduction and platinum(ii) reactions in cancer cells

et al. 2009

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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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“…The precipitate was filtered, washed with water, ethanol, aether, and dried under vacuum. Yield: 78.36% [9] .…”

Section: Preparation Of Complexmentioning

confidence: 99%

Synthesis and antitumor activity of iodo-bridged binuclear platinum complex

et al. 2006

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Iodo-bridged binuclear platinum(II) complex[Pt( -NH 2 )I 2 ] 2 (BPA) has been synthesized and characterized by elemental analysis, conductivity, differential thermal analysis, IR, UV and 1 HNMR spectra techniques. The cytotoxicity of the complex was tested by MTT and SRB assays. The results show that complex BPA demonstrates better cytotoxicity than that of the clinically established cisplatin against EJ, HCT-8, BGC-823, HL-60 and MCF-7 cell lines. The complex BPA at concentrations of 1.00 and 2.00 μmol/L induces G 1 cell cycle arrest in HL-60 cells. The level of total platinum bound to DNA in HL-60 cells is significantly higher than that of cisplatin under the same experimental conditions. Acute toxicity experimental results indiacte that LD 50 of BPA is 815.3 mg/kg by intraperitoneal administration. BPA at dose of 12 mg/kg significantly inhibits the growth of nude mice implanted by human A2780 and HCT-116 carcinomas, and inhibition rate is similar to that of cisplatin at dose of 4 mg/kg by intraperitoneal administration. BPA at dose of 20 mg/kg inhibits the growth of nude mice implanted by human A549 carcinomas, but there was no significant statistical difference.Keywords: iodo-bridged binuclear platinum complex, platinum, cell cycle, antitumor.Cisplatin antitumor activity was discovered in 1967, and cisplatin entered clinical phase I trial in 1971, and was approved for clinical use by the US Food and Drug Administration (FDA) in 1979. Cisplatin is the first metal complex available for the treatment of a variety of malignancies and one of the most active chemotherapeutic agents. Since the introduction of cisplatin, thousands of Pt compounds have been synthesized and evaluated as potential antitumor agents. Much valuable work has also been done in China. Among the 33 platinum complexes which have entered clinical trials after the onset of clinical studies with cisplatin in the early 1970s, only carboplatin has received worldwide approval so far. In addition, some drugs (oxaliplatin, nedaplatin and lobaplatin) have also gained regionally limited approval. Despite their success, they have several disadvantages that include severe toxicity, natural and development resistance and a relatively narrow range of tumors. Because they are small molecules, they only can recognize 2-3 bases and damage easily DNA of normal cells. The binding-force of drug-DNA is very low. After mono-adducts formation, they will induce structure change of DNA (B type → Z type) and significantly decrease antitumor efficiency [1,2] . Now attention has been turned to the synthesis of "non-classical" platinum complexes-binuclear and multinuclear platinum complexes in order to overcome the above shortcomings [3,4] . Farrell [5] have extensively investigated binuclear platinum complexes, particularly the ones with the general formulas [{PtClm (NH 3 ) 3-m }μ-H 2 N-R-NH 2 -{PtCln(NH 3 ) 3-n }] [(2-m)+(2-n)]+ (m or n=0-3, R is a linear or substituted aliphatic linkers). For dicationic complexes with two [PtCl(NH 3 ) 2 (NH 2 R-)] centers, the cis-or tr...

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Synthesis and antitumor activity of ammine/amine platinum(II) and (IV) complexes

Cited by 51 publications

References 12 publications

Investigations using fluorescent ligands to monitor platinum(iv) reduction and platinum(ii) reactions in cancer cells

Investigations using fluorescent ligands to monitor platinum(iv) reduction and platinum(ii) reactions in cancer cells

A study on the genotoxic activities of some new benzoxazoles

Synthesis and antitumor activity of iodo-bridged binuclear platinum complex

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