Radiosensitization by metal complexes of 4(5)-nitroimidazole
Four closely-related cis-platinum (Pt) complexes of 4(5)-nitroimidazole have been examined with respect to properties of radiobiological interest, to test the hypothesis that targeting a nitroimidazole (NO2Im) to DNA could enhance its radiosensitizing ability: I [PtCl2(5-NO2Im)2]; II [PtCl2(4-NO2Im)...
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Published in | International journal of radiation biology Vol. 57; no. 5; p. 947 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
England
1990
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Abstract | Four closely-related cis-platinum (Pt) complexes of 4(5)-nitroimidazole have been examined with respect to properties of radiobiological interest, to test the hypothesis that targeting a nitroimidazole (NO2Im) to DNA could enhance its radiosensitizing ability: I [PtCl2(5-NO2Im)2]; II [PtCl2(4-NO2Im)2]; III [PtCl2(NH3)(5-NO2Im)]; IV [PtCl2(NH3)(4-NO2Im)]. The reduction potential was affected to the same extent on metal binding in all of the complexes (delta E1/2 = +200 mV, cf. ligand measured polographically). Higher sensitization by 5-NO2 complexes I, III (cf. II, IV) was found. Only the mono complexes III and IV bind to DNA (in an assay using inhibition of restriction endonuclease activity); these radiosensitize as well as, or better than, free ligand in hypoxic CHO cells, and better than the bis complexes (I and II). The toxicity of the mono complexes is higher than ligand, and parallels the binding (III, IV, mono bis analogues). The complexes are compared with 4-nitroimidazole complexes of ruthenium, with respect to toxicity, binding and radiosensitization. |
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AbstractList | Four closely-related cis-platinum (Pt) complexes of 4(5)-nitroimidazole have been examined with respect to properties of radiobiological interest, to test the hypothesis that targeting a nitroimidazole (NO2Im) to DNA could enhance its radiosensitizing ability: I [PtCl2(5-NO2Im)2]; II [PtCl2(4-NO2Im)2]; III [PtCl2(NH3)(5-NO2Im)]; IV [PtCl2(NH3)(4-NO2Im)]. The reduction potential was affected to the same extent on metal binding in all of the complexes (delta E1/2 = +200 mV, cf. ligand measured polographically). Higher sensitization by 5-NO2 complexes I, III (cf. II, IV) was found. Only the mono complexes III and IV bind to DNA (in an assay using inhibition of restriction endonuclease activity); these radiosensitize as well as, or better than, free ligand in hypoxic CHO cells, and better than the bis complexes (I and II). The toxicity of the mono complexes is higher than ligand, and parallels the binding (III, IV, mono bis analogues). The complexes are compared with 4-nitroimidazole complexes of ruthenium, with respect to toxicity, binding and radiosensitization. |
Author | Skov, K A Farrell, N P |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/1970996$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1002_ejic_200900054 crossref_primary_10_1007_BF02038230 crossref_primary_10_1016_j_poly_2008_06_035 crossref_primary_10_1080_095530096145760 crossref_primary_10_1039_C8CS00641E crossref_primary_10_1007_BF00139314 crossref_primary_10_1016_j_jelechem_2004_02_030 crossref_primary_10_1016_S0020_1693_96_05537_5 crossref_primary_10_1002_jccs_201300117 crossref_primary_10_1039_C7NJ02061A crossref_primary_10_1248_bpb_28_69 crossref_primary_10_1002_qsar_19950140205 crossref_primary_10_1021_cr980439y |
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Snippet | Four closely-related cis-platinum (Pt) complexes of 4(5)-nitroimidazole have been examined with respect to properties of radiobiological interest, to test the... |
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SubjectTerms | Animals Cell Hypoxia - physiology Cell Survival - drug effects Cell Survival - radiation effects Cricetinae Cricetulus DNA - drug effects DNA - radiation effects In Vitro Techniques Nitroimidazoles - pharmacology Organoplatinum Compounds - pharmacology Radiation-Sensitizing Agents - chemical synthesis Radiation-Sensitizing Agents - pharmacology |
Title | Radiosensitization by metal complexes of 4(5)-nitroimidazole |
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