Cancer lapachol

Some synthetic lapachol derivatives have also showed cytotoxic activity. Burton et al have prepared mono(arylimino) derivatives of P-lapachone. Some of these derivatives had good scores with net cell kills in preliminary in vivo testing hollow fiber assays against a standard panel of 12 human tumor cell lines [160].Twelve substituted 1,4-naphthoquinones were tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis showed that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials [161]. Zalkow et al have synthesized a monoimine quinone, namely 2-methyl-(Z)-4-phenylimino)naphth[2,3-d]oxazol-9-one, which in in vitro tests showed a selective activity for some solid cancer tumors [162]. Enamine derivatives of lapachol were... 

Lapachol (95, from the lapacho tree, genus Tabebuia, family of the catalpa trees, Bignoniaceae) and its analogues show very broad therapeutic capabilities , including activity against cancer which results in apoptosis and inhibition in metastasis, antimicrobial, antifungal, antimalarial and other activities . However, clinical application of lapachol is limited by its high toxicity. Lapachol forms complexes with many metal ions. 

Figure 2 Lapachol occurs in the heartwood of many Tabebuia species. Its interfence in oxidative processes has been documented. Its metabolite fi-lapachone inhibits enzymes associated with DNA replication. However the use of Tabebuia bark (pau d arco) as a cancer preventative can hardly be attributed to these activities.

Block, J., et al.. Early clinical studies with lapachol (NSC-11905), Cancer Chemother. Rep. (1974) 4, 27-28. 

Lapachol and lapachol derivatives exhibited cytotoxicity against A549 human breast cancer cells in vitro. The ICgg of lapachol was 0.78 mM (Oliveira et al. 2002). 

The compounds lapachol and 3-lapachone have been shown to be cytotoxic to cancer cells in animal studies and at micromolar concentrations in vitro in certain human cancer cell lines (Li et al. 1999 Menacho-Marquez and Murguia 2006 Ough et al. 2005 Pardee et al. 2002 Perez-Sacau et al. 2007 Queiroz et al. 2008). 3-lapachone has been shown to have inhibitory activity on DNA topoisomerase (Lee et al. 2005), and cell death may also be caused by activation of a futile cycling of the drug by the cytoplasmic two-electron reductase NAD(P)H quinone oxidoreductase (Ough et al. 2005 Pardee et al. 2002). 

Gupta SR, Malik KK, Seshadri TR 1969 Lapachol from the heartwood of Tecoma undulata and a note on its reactions. Int J Cancer 7 457-459... 

Rao KV, McBride TJ, Oleson JJ 1967 Lapachol as an antitumor agent recognition and evaluation. Proc Amer Assoc Cancer Res 9 55... 

Rao, K. V. Quinone Natural Products. Streptonigrin (NSC-45383) and Lapachol (NSC-11905) Structure-Activity Relationships. Cancer Chemother. Rep. part 4, 4, 11 (1974). 

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