Naphthoquinones antitumor activity

Menadione, or vitamin K3 (VK3), is the synonym for 2-methyl-l,4-naphthoquinone, and does not occur in nature. It has to be synthesized, and acts as an intermediate in synthesis of K vitamins. VK3, as a provitamin, can be transformed to MK4 by micro-organisms. Menadione has been shown to exhibit antitumor activity in rodent and human tumor cells (6-9). A water-soluble form of the provitamin VK3 (menadione sodium bisulfite, MSB see Structures 6 and 7 in Fig. 1) is often added to animal feed, and after treatment with aqueous Na2C03 (destroying the bisulfite salt) and/or irradiation with UV-radiation (10), it can be chromatographed and analyzed in usual ways. 

Because of such extensive application in folk medicine, it is easy to understand the interest that the lapachol, the related naphthoquinones a-lapachone, P-lapachone and other naphthoquinones derivatives, have aroused as potential drugs. In fact, a broad variety of biological activities have been described for this kind of compounds. Some examples are antitumor promoting activities [11-12], inactivators of human cytomegalovirus protease [13], antiprotozoal activity [14], trypanocidal activity [15], anticancer activity [16], and antibacterial and antifungal activities [17]. 

Gokhale et al. [72] have synthesized a series of hydroxynaphthoquinone metal complexes as antitumor agents. The cytotoxic studies against the human breast cancer cell line MCF-7 revealed enhanced activities for the metal complexes. The highest activity is observed for the copper compound of lawsone, Fig. (12) (2-hydroxy-l,4-naphthoquinone). 

LIN, A.J., B.J. LILLIS, A.C. SARTORELLI. 1975. Potential bioreductive alkylating agents. 5. Antineo-plastic activity of quinoline-5,8-dione, naphtha-zarine and naphthoquinones. J. Med. Chem. 18 917. LIN, A.J., A.C. SARTORELLI. 1976. Potential bioreductive alkylating agents. 7. Antitumor effects of phenyl-substituted 2-chloromethyl-3-phenyl-1,4-naphthoquinones. J. Med. Chem. 19 1336. LIN, A.J., A.C. SARTORELLI. 1973. 2,3-Dimethyl-5,6-... 

Hayashi T, Smith FT, Lee KH (1987) Antitumor agents, 89. Psychorubrin, a new cytotoxic naphthoquinone from Psychotria rubra and its structure-activity relationships. J Med Chem 30 2005-2008. doi 10.1021/jm00394a013... 

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