Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria

Abstract

Eight new cardiac glycosides/aglycones (antiaritoxiosides A–G, 1–7, and antiarotoxinin B, 8), two new coumarins (anticarins A–B, 41–42), and two new flavanones (antiarones L–K, 43–44) were isolated from trunk bark of Antiaris toxicaria together with 53 known compounds. The new structures were established by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3α-hydroxy) and compounds 3–6 (10-hydroxy) contain unique substituents that are rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9, CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all ten cancer cell lines, with notable potency at the ng/mL level against some cell lines, which merits further development as clinical trial candidates.

Cardiac Glycoside Constituents of Streblus asper with Potential Antineoplastic Activity

“…Such a retro-Prins-type reaction based mechanism could also be extended to the biosynthesis of other 19-nor cardiac glycosides, as reported from Antiaris toxicaria recently. 36 …”

Three new compounds from the bark of Antiaris toxicaria

“…The other nine known compounds were identified as xanthyletin (4) (Hong et al, 2012), seselin (5) (Hong et al, 2012), umbelliferone (6) (Olennikov et al, 2012), 7-demethylsuberosine (7) (Kang et al, 2001), 8-hydroxy-7-methoxy-6-prenylcoumarin (8) (Filho et al, 1972), vaginol (9) (Zou et al, 2005), antiarsin B (10) (Jiang et al, 2009), antiarone K (11) (Shi et al, 2014), and antiarone F (12) (Hano et al, 1990a) by comparison of their physical and spectroscopic properties with those reported in the literatures.…”

“…Previous chemical investigations of this species have revealed that it was rich in cardiac glycosides, especially from its latex Que et al, 2010) and seed (Zuo et al, 2013). Apart from the cardiac glycosides, prenylflavanones (Hano et al, 1990a,b;Hano et al, 1991;Que et al, 2009), phenylpropanoid and lignan derivatives (Jiang et al, 2009), and coumarin derivatives (Shi et al, 2014) were other kinds of components discovered from this plant, which exhibited anti-osteoporosis (Jiang et al, 2009) and antibacterial activities (Que et al, 2009).…”

“…The absolute configuration of C-2 was determined to be S configuration by a negative cotton effect at 289 nm and a positive cotton effect observed at 331 nm in the circular dichroism (CD) spectrum of 2(Fig. 5)(Antus et al, 1994) (Shi et al, 2014). Thus, compound 2 was established as (2S)-4,5,7-trihydroxy-3 0 -methoxy-2 0 -prenylflavanone named antiarone M.Compound 3 was obtained as colorless oil.…”

Native Medicines and Cardiovascular Toxicity

“…The active components are cardenolides and alkaloids, which include cardiac glycoside, coumarins, and flavanones. 38 The most important toxin is a cardiac glycoside named antiarin. Clinical manifestations are similar to digitalis overdose and the management is supportive.…”