Marine natural products and their synthetic derivatives represent a major source of novel candidate anti-
cancer compounds. We have recently tested the anti-
cancer activity of more than forty novel compounds based on an
iminoquinone makaluvamine scaffold, and have found that many of the compounds exert potent cytotoxic activity against human
cancer cell lines. One of the most potent compounds,
BA-TPQ [(11,12),7-(benzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one], was active against a variety of human
cancer cell lines, and inhibited the growth of breast and prostate xenograft
tumors in mice. However, there was some toxicity noted in the mice following administration of the compound. In order to further the development of
BA-TPQ, and in a search for potential sites of accumulation that might underlie the observed toxicity of the compound, we accomplished preclinical pharmacological studies of the compound. We herein report the in vitro and in vivo pharmacological properties of
BA-TPQ, including its stability in plasma,
plasma protein binding, metabolism by S9
enzymes, and plasma and tissue distribution. We believe these studies will be useful for further investigations, and may be useful for other investigators examining the use of similar compounds for
cancer therapy.