Study on the Cytotoxic Activity of Drimane Sesquiterpenes and Nordrimane Compounds against Cancer Cell Lines

Abstract

Twelve drimanes, including polygodial (1), isopolygodial (2), drimenol (3), confertifolin (4), and isodrimenin (5), were obtained from natural sources. Semi-synthetic derivatives 6-12 were obtained from 1 and 2, and cytotoxic activity was evaluated in vitro against cancer cell lines (HT-29, MDA-MB231, DHF, MCF-7, PC-3, DU-145, and CoN). IC50 values were determined at concentrations of 12.5-100 µM of each compound for 72 h. In addition, it was found that polygodial (1), 8, and 12 induced changes in mitochondrial membrane permeability in CoN, MCF-7, and PC-3 cells.

Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells

“…It should be noted that the potent activity of compound 2 was initially surprising given its recent evaluation by Montenegro against a panel of cancer cell lines, who reported no activity associated with this compound up to 200 μM. 39 However, we retested this compound for using multiple repeats with different assays on a large number of different cells lines as can be seen below and thus are confident in our conclusions.…”

“…However,t he results of mechanistic studies have complicated matters by questioning whether the anticancere ffects of vanilloids are mediated by TRPV1,a nd have revealed that TRPV1 antagonists generally do not prevent vanilloid agonist-induced cell death. [27,[29][30][31][32] Despite severalr eports of cytotoxic activity associated with polygodial, [33][34][35][36][37][38][39] to our knowledge,t his TRPV1 agonist or related bicyclic sesquiterpene dialdehydesh ave not been investigated as potential anticancer agents. This report detailso ur synthetic study of polygodial (1), the generation of as eries of polygodiala nalogues, and the evaluation of the synthesized compounds for TRPV1 and anticancer activities.…”

Semi-synthetic Cinnamodial Analogues: Structural Insights into the Insecticidal and Antifeedant Activities of Drimane Sesquiterpenes Against the Mosquito Aedes aegypti

“…1). Unsaturated dialdehydecontaining compounds exhibit diverse bioactivities 23,24 , including antimicrobial 25 , antifungal 25 , molluscicidal 26 , and cytoxicity 27 . Additionally compounds 1, 2 and 3 are pungent to humans [28][29][30] , possess antifeedant and insecticidal activity 31,32 , and agonize Transient Receptor Potential A1 (TRPA1) channels 21,22,30,33,34 .…”

Semi-synthetic cinnamodial analogues: Structural insights into the insecticidal and antifeedant activities of drimane sesquiterpenes against the mosquito Aedes aegypti

“…Cinnamodial (1) is one of the approximately more than 80 naturally occurring terpenoids containing an α,ß-unsaturated 1,4-dialdehyde functionality [41], specifically 1 belongs to the drimane sesquiterpene class of compounds which includes the structurally similar compounds: warburganal (2) and polygodial (3) (Fig 1). Unsaturated dialdehyde-containing compounds exhibit diverse bioactivities [42,43], including antimicrobial [44], antifungal [44], molluscicidal [45], and cytotoxicity [46]. Additionally compounds 1, 2 and 3 are pungent to humans [47][48][49], possess antifeedant and insecticidal activity [50,51], and agonize Transient Receptor Potential A1 (TRPA1) channels [21,41,49,52,53].…”