A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition.

Phytochemical study of the ethyl acetate root extract of Zygophyllum album has resulted in the isolation of a new saponin, Zygo-albuside D ( 1 ), along with two known compounds; (3-O-[β-D-quinovopyranosyl]-quinovic acid) ( 2 ), which is first reported in the root, and catechin ( 3 ), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin ( 1 ) exhibited promising cytotoxicity with IC 50 values of 3.5 and 5.52 μM on A549 and PC-3 cancer cell lines, respectively, compared to doxorubicin with IC 50 values of 9.44 and 11.39 μM on A549 and PC-3 cancer cell lines, respectively. While it had an IC 50 value of 46.8 μM against WISH cells. Investigating apoptosis-induction, compound 1 induced total apoptotic cell death in A549 lung cancer cells by 32-fold; 21.53% compared to 0.67% in the untreated control cells. Finally, it upregulated the pro-apoptotic genes and downregulated the antiapoptotic gene using gene expression levels. Compound 1 exhibited remarkable CDK-2 target inhibition by 96.2% with an IC 50 value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound 1 as CDK2 and Bcl2 inhibitors that led to apoptosis induction in A549 cancer cells. Hence, this study highlights the importance of compound 1 in the design of a new anticancer agent with specific mechanisms.