beta-Lapachone: synthesis of derivatives and activities in tumor models.
In order to find a 3,4-dihydro-2H-naphtho[1,2-b]pyran-5,6-dione more potent than the naturally occurring 2,2-dimethyl derivative [beta-lapachone (10a)], we synthesized a series of analogous compounds with modifications at position 2 of the pyran ring or at positions 8 and 9 of the benzene ring. Of the compounds tested in vitro for inhibition of RNA-dependent DNA polymerase and in mice infected with Rauscher leukemia, all retained good enzyme activity. Inhibition of the reverse transcriptase activity of the 2,2-substituted derivatives 10b-e was as strong as 10a. However, only the 2-methyl-2-phenyl derivative 10e proved to be about as potent as the 2,2-dimethyl reference compound 10a in prolonging the mean survival time of mice with Rauscher leukemia virus induced leukemia.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000627:therapeutic use; D011925:Rauscher Virus; D018894:Reverse Transcriptase Inhibitors
D000903:Antibiotics, Antineoplastic; D009285:Naphthoquinones; D018894:Reverse Transcriptase Inhibitors; C014638:beta-lapachone