The relatively simple naphthoquinone -lapachol (119;
Scheme 21) is a well-known compound obtained from the
bark of the lapacho tree, Tabebuia aVellanedae, and other
species of the same genus that are native to South America.
-Lapachol and other plant components are extensively used
as ethnobotanical treatments in the Amazonian region, and
-lapachol was advanced to clinical status by the National
Cancer Institute (NCI) in the 1970s. It was later withdrawn
due to unacceptable levels of toxicity, but its close relative
-lapachone (120; Scheme 21) has demonstrated interesting
molecular target activity, with one mechanism of action being
the induction of apoptosis in transformed cells.323 Evidence
of its involvement in transcription processes has been
reported, demonstrating that the agent induced activation of
caspase-3, inhibition of NFκB, and subsequent downregulation
of bcl-2.324 Currently, -lapachone (ARQ501) is in
phase II clinical trials in the U.S.A. for advanced solid
tumors, and further information on the background of these
agents may be obtained from a 2004 review.
The relatively simple naphthoquinone -lapachol (119;
Scheme 21) is a well-known compound obtained from the
bark of the lapacho tree, Tabebuia aVellanedae, and other
species of the same genus that are native to South America.
-Lapachol and other plant components are extensively used
as ethnobotanical treatments in the Amazonian region, and
-lapachol was advanced to clinical status by the National
Cancer Institute (NCI) in the 1970s. It was later withdrawn
due to unacceptable levels of toxicity, but its close relative
-lapachone (120; Scheme 21) has demonstrated interesting
molecular target activity, with one mechanism of action being
the induction of apoptosis in transformed cells.323 Evidence
of its involvement in transcription processes has been
reported, demonstrating that the agent induced activation of
caspase-3, inhibition of NFκB, and subsequent downregulation
of bcl-2.324 Currently, -lapachone (ARQ501) is in
phase II clinical trials in the U.S.A. for advanced solid
tumors, and further information on the background of these
agents may be obtained from a 2004 review.
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