The Cytotoxic Cardiac Glycoside (−)-Cryptanoside A from the Stems ofCryptolepis dubiaand Its Molecular Targets

Abstract

A cardiac glycoside epoxide, (−)-cryptanoside A (1), was isolated from the stems of Cryptolepis dubia collected in Laos, for which the complete structure was confirmed by analysis of its spectroscopic and single-crystal X-ray diffraction data, using copper radiation at a low temperature. This cardiac glycoside epoxide exhibited potent cytotoxicity against several human cancer cell lines tested, including HT-29 colon, MDA-MB-231 breast, OVCAR3 and OVCAR5 ovarian cancer, and MDA-MB-435 melanoma cells, with the IC50 values found to be in the range 0.1–0.5 μM, which is comparable with that observed for digoxin. However, it exhibited less potent activity (IC50 1.1 μM) against FT194 benign/nonmalignant human fallopian tube secretory epithelial cells when compared with digoxin (IC50 0.16 μM), indicating its more selective activity toward human cancer versus benign/nonmalignant cells. (−)-Cryptanoside A (1) also inhibited Na+/K+-ATPase activity and increased the expression of Akt and the p65 subunit of NF-κB but did not show any effects on the expression of PI3K. A molecular docking profile showed that (−)-cryptanoside A (1) binds to Na+/K+-ATPase, and thus 1 may directly target Na+/K+-ATPase to mediate its cancer cell cytotoxicity.

Four New Pentacyclic Triterpene Glycosides Isolated from the Fruits of Cryptolepis buchananii R.Br. ex Roem. & Schult and Their Inhibition of NO Production in LPS‐activated RAW264.7 Cells

“…[1][2][3][4] According to published studies, the plant contains saponins, terpenoids, alkaloids, tannins, phenolics, and steroids. [4][5][6][7][8][9][10] The aerial parts of this plant are used for its anti inflammatory, antibacterial, anticough, antidiarrheal, demulcent, diaphoretic, antiulcerative, and diuretic properties. [1][2][3][4]10] In Vietnam, this plant widely distributed in Dakrong, Quang Tri, Ninh Binh, Nghe An, Hanoi, Hanam, Ha Tay, Vinh Phu, Dong Nai, Tay Ninh, Ba Ria-Vung Tau, An Giang provinces and used in the folk medicine to treat wounds, primples, and infections.…”

“…The entire tree has latex and is poisonous and used as folk medicine in southeast Asia [1–4] . According to published studies, the plant contains saponins, terpenoids, alkaloids, tannins, phenolics, and steroids [4–10] . The aerial parts of this plant are used for its anti inflammatory, antibacterial, anticough, antidiarrheal, demulcent, diaphoretic, antiulcerative, and diuretic properties [1–4,10] .…”