Cytotoxicity of Poupartone B, an Alkyl Cyclohexenone Derivative from Poupartia borbonica, against Human Cancer Cell Lines

Abstract

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A – C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp., high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 – 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed.

Bioactive Clerodane Diterpenoids from the Leaves of Casearia coriacea Vent

“…Considering the above-mentioned elements, a large screening of 64 endemic plants of the Mascarene Islands was carried out by our team and highlighted the potential of some plants, including Poupartia borbonica [ 8 , 9 , 10 ], Vernonia fimbrillifera [ 11 ], as well as Casearia coriacea [ 12 ]. The present study describes the bioassay-guided fractionation of Casearia coriacea that was achieved with the P. falciparum strain.…”

Stereospecific Synthesis of Cyclohexenone Acids by [3,3]-Sigmatropic Rearrangement Route

“…Chiral cyclohexenones are core structures in many natural products and pharmaceuticals, − and therefore important targets for synthetic chemistry. − Commonly employed synthetic strategies for chiral cyclohexenones include Robinson annulations, , Michael additions, − and aldol condensations , together with recent examples including homo-Nazarov cyclization and 1,3 protonic shift . [3,3]-sigmatropic rearrangements are a convenient way to achieve regio- and stereoselective C–C and C–X bond forming reactions in organic chemistry. − Notably, the [3,3]-sigmatropic rearrangement approach is largely an unexplored option for cyclohexenone synthesis.…”

Access to Functionalized Cyclohex-2-enones from a Multicomponent Cascade Reaction of Readily Available Alkynes, Ketones, and Ethyl Acetoacetate

“…5−7 Recently, cyclohex-2-enone derivatives have attracted a considerable amount of attention 8−10 due to their potential applications in drug design and the medicinal industry. The biological activities of many compounds bearing a cyclohex-2-enone moiety have been well established, such as anti-inflammatory, 11 antibacterial, 12−14 anticancer, 15 and antimalarial 16 activities.…”

“…Cascade or tandem processes are one-pot multistep reactions that provide concise approaches to complex structures, and hence, they are powerful for synthetic transformations. − Cascade reactions are environmentally benign and economically efficient because they minimize waste, energy, labor, and time because the intermediates are not isolated and purified. − Recently, cyclohex-2-enone derivatives have attracted a considerable amount of attention − due to their potential applications in drug design and the medicinal industry. The biological activities of many compounds bearing a cyclohex-2-enone moiety have been well established, such as anti-inflammatory, antibacterial, − anticancer, and antimalarial activities.…”