Synthesis of novel naphthoquinone-spermidine conjugates and their effects on DNA-topoisomerases I and II-alpha

Journal of the Brazilian Chemical Society

Andréa S. Cunha²  Edson L. S. Lima²  Angelo C. Pinto²  Andressa Esteves-souza²  Aurea Echevarria¹  Celso A. Camara¹  Maria D. Vargas¹  José C. Torres¹ 

[1] ,Universidade Federal do Rio de Janeiro Instituto de Química Rio de Janeiro RJ ,Brazil

关键词: spermidine;    lapachol;    lawsone;    nor-lapachol;    DNA-topoisomerase II-alpha;   

DOI  :  10.1590/S0103-50532006000300002

来源: SciELO

【 摘 要 】

Novel derivatives of lapachol 2, nor-lapachol 3 and lawsone 4 have been synthesized by nucleophilic displacement of the methoxynaphthoquinones 2a, 3a and 4a with the polyamine (PA) N¹-Boc-N5-Bn-spermidine 1a. The respective products 2b-4b were obtained in good yields and characterized by spectroscopic and analytical methods. The inhibitory action of these naphthoquinone-PA conjugates on DNA-topoisomerases (topo) I and II-alpha was evaluated by relaxation assay of supercoiled DNA plasmid. All compounds (1a 2b, 3b and 4b) presented significant inhibition of topo II-alpha catalytic activity at the 2 µM dose. Considering that only PA 1a did not inhibit the enzyme catalytic activity at the 0.2 µM dose, the appended naphthoquinone moiety acts as a "value added" fragment. Compounds 1a 2b, 3b and 4b did not inhibit the enzyme DNA-topo I at the 200 µM dose.

【 授权许可】

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