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. 2023 Dec 29;29(1):199.
doi: 10.3390/molecules29010199.

Bio-Guided Assay of Ephedra foeminea Forssk Extracts and Anticancer Activities: In Vivo, In Vitro, and In Silico Evaluations

Jilan A Nazeam  1 , Sylvia A Boshra  2 , Esraa Z Mohammed  3 , Heba A El Gizawy  1
Affiliations

Bio-Guided Assay of Ephedra foeminea Forssk Extracts and Anticancer Activities: In Vivo, In Vitro, and In Silico Evaluations

Jilan A Nazeam et al. Molecules. .

Abstract

Ephedra is one of the oldest known medicinal plants and the largest genera of the Ephedraceae family. In vivo antitumor evaluation of Ephedra foeminea revealed that ethyl acetate (EtOAc) was the most bioactive fraction. Bio-guided fractionation of EtOAc fraction afforded nine compounds isolated for the first time from the plant species. Macrocyclic spermine alkaloids (1,9), proanthocyanidins (2,4,5), quinoline alkaloids (7,8), phenolic (3), and nucleoside (6) were identified and elucidated by spectroscopic analyses including 1D and 2D NMR, ESI-MS-MS spectrometry. The tested compounds exhibited moderate anticancer activity, except for the kynurenic acid derivative (6-mKYNA) which showed significant cytotoxicity and remarkable inhibition of CA-19.9 and CA-125 tumor biomarkers. In-silico study was conducted to determine the anti-proliferative mechanism of 6-mKYNA by using the CK2 enzyme active site. Moreover, the ADME computational study suggested that 6-mKYNA is an effective candidate with a promising pharmacokinetic profile and therapeutic potential against various types of cancer.

Keywords: 6-methoxykynurenic acid; ADME; Ephedra foeminea; alkaloids; in silico; proanthocyanidins; tumor marker.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effect of E. foeminea Forssk fractions (hexane, dichloromethane, ethyl acetate, and methanol fractions) and 5FU on plasma CA-19.9 (A) and CA-125 (B) in the normal group (I) and Ehrlich ascites carcinoma-bearing mice groups (II–VII). Letters (a–g) indicate significant differences at p ≤ 0.05. Data followed by the same letter are not significantly different at p ≤ 0.05.
Figure 2
Figure 2
Structures of the isolated compounds 1–9.
Figure 3
Figure 3
2D ligand interaction diagram of the re−docked pose in the CK2 binding site.
Figure 3
Figure 3
2D ligand interaction diagram of the re−docked pose in the CK2 binding site.
Figure 4
Figure 4
Ligand interaction diagram of 6-mKYNA (8) with the CK2 ATP binding site in 2D representation (A) and 3D representation (B).
Figure 5
Figure 5
Human intestinal absorption (HIA) and blood−brain barrier (BBB) plots for all studied 6−mKYNA.
See this image and copyright information in PMC

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