7-epi-Clusianone, a Multi-Targeting Natural Product with Potential Chemotherapeutic, Immune-Modulating, and Anti-Angiogenic Properties

Abstract

Targeted therapies have changed the treatment of cancer, giving new hope to many patients in recent years. The shortcomings of targeted therapies including acquired resistance, limited susceptible patients, high cost, and high toxicities, have led to the necessity of combining these therapies with other targeted or chemotherapeutic treatments. Natural products are uniquely capable of synergizing with targeted and non-targeted anticancer regimens due to their ability to affect multiple cellular pathways simultaneously. Compounds which provide an additive effect to the often combined immune therapies and cytotoxic chemotherapies, are exceedingly rare. These compounds would however provide a strengthening bridge between the two treatment modalities, increasing their effectiveness and improving patient prognoses. In this study, 7-epi-clusianone was investigated for its anticancer properties. While previous studies have suggested clusianone and its conformational isomers, including 7-epi-clusianone, are chemotherapeutic, few cancer types have been demonstrated to exhibit sensitivity to these compounds and little is known about the mechanism. In this study, 7-epi-clusianone was shown to inhibit the growth of 60 cancer cell types and induce significant cell death in 25 cancer cell lines, while simultaneously modulating the immune system, inhibiting angiogenesis, and inhibiting cancer cell invasion, making it a promising lead compound for cancer drug discovery.

Unusual derivatives from Hypericum scabrum

“…The aforementioned data indicated some structural aspects of 7- epi -clusianone ( 4 , Fig. 5 ), a BPAP with a normal bicyclo[3.3.1]-nonane core 25 , that was also isolated in this study 26 . The main spectral differences between 1 and 4 were due to the significant variations in the NMR data of the perenyl group at C-1, replacement of a benzylic ketone at δ C 197.7 with a benzylic ester at δ C 165.6, and replacement of an enolic carbon at δ C 196.5 with a ketonic one at δ C 200.9.…”

Andrographis paniculata (Burm. f.) Wall. ex Nees: An Updated Review of Phytochemistry, Antimicrobial Pharmacology, and Clinical Safety and Efficacy

“…Nowadays, the philosophy of drug discovery has transformed into "one drug, multitarget" from "one drug, one target" [16,[21][22][23][24][25][26][27][28]. Plant-derived secondary metabolites hold the potential of multi-targeting properties as they need to undergo evolving defence mechanisms of the plant against predators like bacteria, fungi, virus, even insects and herbivores [15,16,21,22,29,30]. A majority of the world population relies on medicinal plants for first-line treatment due to the severe side effects of synthetic drugs [31].…”

The Synthesis of Novel Aminoacid Based Amides and Evaluation of Anticancer Effects on Hela Cervical Cancer Cells

“…The main treatment approach to be done with chemotherapeutics is to induce apoptosis and prevent metastasis by suppressing vascularity. Many studies have been reported on this treatment approach today (Abbas et al, 2020;Zhong et al, 2020;Taylor et al, 2019;Gagic et al, 2016). In this study, the chemotherapeutic effects of amides synthesized by our research team were investigated on HeLa cervical cancer cells.…”