Phytochemical investigation of Egyptian Spinach leaves, a potential source for antileukemic metabolites: in vitro and in silico study

Authors: ABDELGAWAD, SHIMAA - University Of Mississippi; HETTA, MONA - El-Fayoum University; IBRAHIM, MOHAMED - University Of Mississippi; BALACHANDRAN, PREMALATHA - University Of Mississippi; ZHANG, JIN - University Of Mississippi; Wang, Mei; FAWZY, GHADA - Cairo University; EL-ASKARY, HESHAM - Cairo University; ROSS, SAMIR - University Of Mississippi

Submitted to: Revista Brasileira de Farmacognosia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/30/2022
Publication Date: 9/22/2022
Citation: Abdelgawad, S.M., Hetta, M.H., Ibrahim, M.A., Balachandran, P., Zhang, J., Wang, M., Fawzy, G.A., El-Askary, H.I., Ross, S.A. 2022. Phytochemical investigation of Egyptian Spinach leaves, a potential source for antileukemic metabolites: in vitro and in silico study. Revista Brasileira de Farmacognosia. https://doi.org/10.1007/s43450-022-00307-0.
DOI: https://doi.org/10.1007/s43450-022-00307-0

Interpretive Summary: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that is characterized by uncontrolled myeloid cell divisions in the bone marrow. Several secondary metabolites from natural origin such as alkaloids, flavonoids, terpenoids, and polyketides exhibited a potent anti-CML activity. Spinacia oleracea L. (SO) is an annual popular winter vegetable crop that is widely cultivated in Egypt. Spinach is considered as a vegetable with a high biological value due to the presence of secondary metabolites from various chemical classes with a wide range of biological effects including antioxidant, anti-inflammatory, antiproliferative, hypolipidemic, and CNS suppressant properties. The aim of this study is to carry out detailed phytochemical and biological investigations of SO leaves. Phytochemical study of SO ethyl acetate fraction resulted in the isolation of two new flavone C-glycosides: isoswertisin -3''-O-xyloside and vitexin 3''-O-xyloside, alongside with three known compounds, viz. methyl myristate, 9-hexadecenoic acid methyl ester, and methyl hexadec-11-enoate. The biological study revealed that these three compounds exhibited a remarkable antiproliferative activity against K562 cells in vitro. In Silico mechanistic study also showed that these three compounds exhibited a strong binding affinity towards Abl Kinase.

Technical Abstract: Based on our previous biological screening of certain Egyptian edible leafy vegetables against leukemia K562 cell line, Spinacia oleracea (SO) leaves demonstrated a potential antileukemic activity. Thus, the aim of this study is to carry out detailed phytochemical and biological investigations of SO leaves cultivated in Egypt. Bio-guided study of the n-hexane fraction using GC/MS analysis resulted in the identification of twenty-five compounds in the saponifiable matter and the isolation of twelve compounds (1-12) from the unsaponifiable matter. Phytochemical study of SO ethyl acetate fraction resulted in the isolation of two new flavone C-glycosides: isoswertisin -3''-O-xyloside (13) and vitexin 3''-O-xyloside (14), alongside with three known compounds. The biological study revealed that compounds (1, 4, and 6) exhibited a remarkable antiproliferative activity against K562 cells invitro. In Silico mechanistic study showed that compounds (1, 4, and 6) exhibited a strong binding affinity towards Abl Kinase (docking score = -8.5523, -7.6724 and -9.6475 Kcal/Mole, respectively). Moreover, compound (1) showed a strong binding affinity towards topoisomerase (docking score = -8.4926 and Kcal/Mole).