Title:Acetogenins as Potential Anticancer Agents
Volume: 16
Issue: 2
Author(s): Manu Mangal, Mohd Imran Khan and Subhash Mohan Agarwal
Affiliation:
Keywords:
Acetogenins, asimicin, bullatacin, cancer, multidrug resistance, natural products.
Abstract: Acetogenins (ACG) are naturally occurring compounds that are chemically one of the least investigated
families. In the review, we have provided a comprehensive listing of 133 of these compounds for which anti-tumor
activity has been documented within the literature. We have compiled and studied their chemical structure, in-vitro
as well as in-vivo anticancer biological activity. We observed that the relative potency of acetogenins can be
categorized as adjacent bis-THF ACGs > nonadjacent bis-THF ACGs > mono-THF ACGs > linear-THF ACGs.
Among adjacent bis-THF ACGs, asiminocin (A100), asiminecin (A101), asiminacin (A102) and asimin (A103)
are the most active compounds with in-vitro activity (ED50) in the range of 10-9 to 10-12 μg/mL. For the
nonadjacent bis-THF ACGs, gigantecin (A53) exhibited better cytotoxicity as compared to others in the series
with an ED50 in the range of 10-6 to 10-8 μg/mL. Similarly, muricatetrocin-C (A36), a mono-THF and coriadienin
(A116) a linear ACG has been reported to show promising cytotoxicity with an ED50 of 10-5 μg/mL. Moreover,
in-vivo studies indicate that compounds like bullatacin (A83), desacetyluvaricin (A76), bullatalicin (A58) and
annonacin (A8) have demonstrated significant activity in mouse models and thereby exhibiting potential for lead
development as a potential anticancer agent/drug. Also, globally oncologists are looking towards compounds from natural origin that
inhibits the growth of resistant tumor cells. We find that several acetogenins like bullatacin (A83), motrilin (A95), asimicin (A77),
trilobacin (A96), annonacin (A8), gigantetronenin (A108) and squamocin (A73) are efficacious in suppressing the proliferation of the
MDR MCF-7/Adr cells. The present analysis suggests that acetogenins can act as yet another important source for obtaining promising
lead compounds in order to contribute to cancer prevention, however, in future extensive in-vivo studies in animal models will be needed
to provide insight for lead development.