title: Cytotoxic and DNA-topoisomerase effects of lapachol amine derivatives and interactions with DNA.
abstract: The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 +/- 1.25 microM, and against K562 leukemia, with IC50 = 14.11 +/- 1.39 microM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 +/- 2.3 microM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 microM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 microM and a partial inhibitory action was observed for lapachol and methoxylapachol.
authors: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brasil.
authors: A
authors: A
authors: Esteves-Souza
authors: D V
authors: DV
authors: Figueiredo
authors: A
authors: A
authors: Esteves
authors: C A
authors: CA
authors: Câmara
authors: M D
authors: MD
authors: Vargas
authors: A C
authors: AC
authors: Pinto
authors: A
authors: A
authors: Echevarria
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology*; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells / Q000187:drug effects; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D059005:Topoisomerase II Inhibitors; D014750:Vincristine; D011794:Quercetin; C008252:lapachol