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    題名: Covalent Interaction of Ru(terpy)(tmephen)Cl+ with DNA: A Potential Ruthenium-Based Anticancer Drug
    作者: 鄭建中;Cheng, Chien-chung;Lee, Wen-li;Su, Chien-kuo;Liu, Chen-lun
    貢獻者: 淡江大學化學學系
    日期: 2000-02-01
    上傳時間: 2013-07-29 13:45:08 (UTC+8)
    出版者: 臺北市:中國化學學會
    摘要: The use of ruthenium complexes in antitumor therapy was launched two decades ago. In view of their low toxicity and good selectivity for solid tumor metastasis, ruthenium complexes have great potential as alternative drugs to cisplatin in cancer chemotherapy. A series of monochloro ruthenium complexes, Ru(terpy) (NN)Cl+ (NN, bidentate nitrogen ligand), containing different electron-donating groups were prepared. The reactivity towards the formation of Ru-DNA adduct were revealed by gel mobility shift assay. Their DNA binding sites of Ru(terpy)(tmephen)Cl+ were located predominantly at the purine residues I.e., guanine and adenine, by terminating DNA elongation in vitro using PCR and primer extension techniques. Surprisingly, the ability of Ru(terpy)(tmephen)Cl+ to inhibit cell growth was found to be approximately two times better than that of a known cross-linking agent, Ru(bpy)2Cl2. Therefore, the increase in liability of the chloro ligand was demonstrated to improve the reactivity of these ruthenium complexes towards the covalent bond formation in Ru-DNA adducts and result also in a significant inhibition of cell growth. Based on our results, these ruthenium complexes modified with electron-rich groups provide new consideration in the tune of ruthenium-based drugs in cancer chemotherapy.  The use of ruthenium complexes in antitumor therapy was launched two decades ago. In view of their low toxicity and good selectivity for solid tumor metastasis, ruthenium complexes have great potential as alternative drugs to cisplatin in cancer chemotherapy. A series of monochloro ruthenium complexes, Ru(terpy) (NN)Cl+ (NN, bidentate nitrogen ligand), containing different electron-donating groups were prepared. The reactivity towards the formation of Ru-DNA adduct were revealed by gel mobility shift assay. Their DNA binding sites of Ru(terpy)(tmephen)Cl+ were located predominantly at the purine residues I.e., guanine and adenine, by terminating DNA elongation in vitro using PCR and primer extension techniques. Surprisingly, the ability of Ru(terpy)(tmephen)Cl+ to inhibit cell growth was found to be approximately two times better than that of a known cross-linking agent, Ru(bpy)2Cl2. Therefore, the increase in liability of the chloro ligand was demonstrated to improve the reactivity of these ruthenium complexes towards the covalent bond formation in Ru-DNA adducts and result also in a significant inhibition of cell growth. Based on our results, these ruthenium complexes modified with electron-rich groups provide new consideration in the tune of ruthenium-based drugs in cancer chemotherapy.
    關聯: Journal of the Chinese Chemical Society=中國化學會會誌 47(1), pp.213-220
    DOI: 10.1002/jccs.200000025
    顯示於類別:[化學學系暨研究所] 期刊論文

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