Hydroxyl Macrocyclic Polyamines Coordination Systems Interaction with DNA and Their Antitumor Activities in vitro

Abstract

Abstract: The interaction between plasmid DNA (pBR322 DNA) and Ni(Ⅱ), Ca(Ⅱ), Co(Ⅱ), Cu(Ⅱ) coordination systems of 3-hydroxyl-1,5,8-triaazacyclic amine (L1) and 3,13-dihydroxyl-1,5,8,11,15,18-hexaazacyclic amine (L2) with several molar ratios were investigated by agarose gel electrophoresis. The results suggested that M L1, M L2 and 2M L2 systems could catalyze the cleavage of supercoiled pBR322 DNA to the nicked and the linear form at the same time under near neutral conditions at 37 ℃. The efficiency of DNA cleavage decreased in the order 2M-L2>M-L2, because there was probably cooperativity between two metal ions in 2M-L2 systems which catalyzed the cleavage of DNA. The little cleavage was found under a comparable conditions by the metal ions or receptor alone. The antitumor activities of two receptors, metal ions and their metal coordination systems were all measured against BEL 7402 cell lines by using MTT assay. The metal ions have cytotoxicity to cells at 10^-3mol/L ; but when it was diluted to 10^-4mol/L, the percentage inhibition decreased sharply. On the contrary, the metal coordination systems still kept their antitumor activities even at 10^-5mol/L. Thus, these coordination systems may be useful as artificial restriction enzymes and may be usefully applied to the development of antitumor drug.

Key words: Macrocyclic polyamines, DNA cleavage, Antitumor activity

CLC Number:

O614.1
R

TrendMD:

LIANG Feng, WEI Jun, LI Zhao-Yang, WU Cheng-Tai, ZHENG Cong-Yi, SUN Meng-Xiang . Hydroxyl Macrocyclic Polyamines Coordination Systems Interaction with DNA and Their Antitumor Activities in vitro[J]. Chem. J. Chinese Universities, 2004, 25(3): 470.

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Hydroxyl Macrocyclic Polyamines Coordination Systems Interaction with DNA and Their Antitumor Activities in vitro

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