Acetogenins as Potential Anticancer Agents

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.

Pharmacokinetic profiling of anticancer phytocompounds using computational approach

“…Naturally occurring compounds of different kinds, such as quinones, terpenoids, alkaloids, flavonoids, etc. are known to play an important role in the prevention of growth of cancerous cells . For example; Vinca alkaloids (tubulin inhibitors) from Catharanthus roseus , and the terpene paclitaxel from Taxus brevifolia are successful anticancer drugs .…”

“…are known to play an important role in the prevention of growth of cancerous cells. [8][9][10] For example; Vinca alkaloids (tubulin inhibitors) from Catharanthus roseus, and the terpene paclitaxel from Taxus brevifolia are successful anticancer drugs. 7 Plants are thus reserves of biologically active molecules that can be developed into pharmacophores with diverse chemical scaffolds and can aid in the process of drug discovery.…”

Correlation Between Acetogenin Content and Antiproliferative Activity of Pawpaw (Asimina triloba [L.] Dunal) Fruit Pulp Grown in Korea

“…The acetogenin asimicin isolated from the stem bark of pawpaw, was found to be cytotoxic toward HT-29 colon cancer cells (Zhao, Miesbauer, Smith, & McLaughlin, 1994), and the acetogenin trilobacin in pawpaw leaves exerted antiproliferative effects in PC-3 prostate cancer and PACA-2 pancreatic cancer cells (Zhao, Chao, Zeng, Rieser, & McLaughlin, 1996). In this way, acetogenins act as important natural materials for preventing various human cancers (Mangal, Khan, & Agarwal, 2016). However, the contents of phytochemical compounds, such as acetogenins, can differ according to chemical, environmental, and agronomic parameters (Donno et al, 2012).…”

Allelopathic and Biochemical Characteristics of the Root Environment of Asimina Triloba (L.) Dunal

“…Asimina triloba (L.) Dunal (pawpaw) is a promising new ornamental and fruit crop for dissemination on Ukraine territory, including botanical gardens, arboretums, farms, etc. Pawpaw is rich in various bioactive compounds, due to which it possesses valuable nutritional, antioxidant, insecticidal, medicinal, including anti-tumoral, properties, as well as high adaptive potential to adverse environmental factors (Cuendet et al, 2008;Farag, 2009;Pande and Akoh, 2010;Sedlacek et al, 2010;Ferreira et al, 2011;Brannan et al, 2015;Ortutu et al, 2015;Koul, 2016;Levon and Klymenko, 2016;Mangal et al, 2016;Avula et al, 2018;Nam et al, 2018a).…”