Presenter: Ospanov Meirambekhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1013/thumbnail.jp

Abdelgawad, Shimaa M.

Balachandran, Premalatha

El-Askary, Hesham I.

Fawzy, Ghada A.

Hetta, Mona H.

Ibrahim, Mohamed A.

Ospanov, Meirambek

Ross, Samir A.

Wang, Mei

Zhang, Jin

English

eGrove (Univ. of Mississippi)

University of Mississippi eGrove Annual Poster Session 2021 Annual Poster Session 10-19-2021 Abl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia Shimaa M. Abdelgawad University of Mississippi Mona H. Hetta University of Mississippi Mohamed A. Ibrahim University of Mississippi Premalatha Balachandran University of Mississippi Jin Zhang University of Mississippi See next page for additional authors Follow this and additional works at: https://egrove.olemiss.edu/pharm_annual_posters_2021 Recommended Citation Abdelgawad, Shimaa M.; Hetta, Mona H.; Ibrahim, Mohamed A.; Balachandran, Premalatha; Zhang, Jin; Wang, Mei; Ospanov, Meirambek; Fawzy, Ghada A.; El-Askary, Hesham I.; and Ross, Samir A., "Abl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia" (2021). Annual Poster Session 2021. 14. https://egrove.olemiss.edu/pharm_annual_posters_2021/14 This Book is brought to you for free and open access by the Annual Poster Session at eGrove. It has been accepted for inclusion in Annual Poster Session 2021 by an authorized administrator of eGrove. For more information, please contact egrove@olemiss.edu. Authors Shimaa M. Abdelgawad, Mona H. Hetta, Mohamed A. Ibrahim, Premalatha Balachandran, Jin Zhang, Mei Wang, Meirambek Ospanov, Ghada A. Fawzy, Hesham I. El-Askary, and Samir A. Ross This book is available at eGrove: https://egrove.olemiss.edu/pharm_annual_posters_2021/14 Based on our previous biological screening of certain Egyptian edible leafy vegetablesagainst leukemia K562 cell line, Spinacia oleracea (SO) leaves demonstrated a potentialantileukemic activity. Thus, the aim of this study is to carry out detailed phytochemicaland biological investigations of SO leaves cultivated in Egypt. Bio-guided study of the n-hexane fraction using GC/MS analysis (Table 1 and 2) resulted in the identification oftwenty-five compounds in the saponifiable matter and the isolation of twelve compounds(1-12) from the unsaponifiable matter. Phytochemical study of SO ethyl acetate fractionresulted 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 biologicalstudy revealed that compounds (1, 4, and 6) exhibited a remarkable antiproliferativeactivity 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 strongbinding affinity towards topoisomerase (docking score = -8.4926 and Kcal/Mole). As aresult of our findings, we recommend the incorporation of spinach leaves in the foodregimen for chronic myeloid leukemia (CML) patients.ABSTRACTAbl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia Shimaa M. Abdelgawad1, Mona H. Hetta, Mohamed A. Ibrahim1, Premalatha Balachandrana1 , Jin Zhang1, Mei Wang1, Ospanov Meirambek1, Ghada A. Fawzy, Hesham I. El-Askary and Samir A. Ross1,2 11National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS 38677, USA2Biomolecular Sciences, Division of Pharmacognosy, School of Pharmacy, University of Mississippi, 38677, United States GENERAL SCHEMEMOLECULAR DOCKING This work was supported by the Egyptian Ministry of Higher Education Missions Sector (grant no. JS-3770).Support from National Center for Natural Products research (NCNPR), University of Mississippi is gratefullyacknowledged.GC/MS ANALYSISACKNOWLEDGMENTSCONCLUSIONSThe n-hexane fraction of Egyptian Spinach leaves as well as its isolated compounds; Hexaprenol(1), Phytol (4) and 18-[(1-Oxohexadecyl) oxy]-9-octadecenoic acid (6) showed remarkableantiproliferative activity against leukemia K562 cell line. The molecular docking study revealed thatthis activity is supposed to be through targeting Abl kinase and topoisomerase, and this still needs tobe proved by in vitro assay of these compounds against the mentioned targets. As a result of ourfindings, we recommend the incorporation of Spinach leaves in the food regimen for the CMLpatients(4) (6)                        Rebastinib(1)Fig.1.Binding affinity of compounds (1, 4, and 6) isolated from SO leaves compared to Rebastini against Abl kinaseFig.2. Binding affinity of compound (1) isolated from SO leaves compared to Etoposide against topoisomerase(1) Etoposide Table 1 Results of GC/MS analysis of fatty acid methyl ester (FAME) of the n-hexane fraction of SO leavesComp. No. Compound Name RT (min)Mol Weight (amu)Peak area (%)1. Methyl myristate 27.8 242.225 0.702. Methyl pentadecanoate 30.4 256.24 0.573. Phytone 30.7 268.277 0.474. (Z)-9-Hexadecenoic acid, methyl ester 32.7 268.24 0.515. Methyl palmitate 33.1 270.256 24.096. (Z)-Methyl hexadec-11-enoate 33.3 268.24 2.407. 7,10,13-Hexadecatrienoic acid, methyl ester 33.4 264.209 0.778. Palmitic acid 34.2 256.24 0.289. Methyl margarate 35.4 284.272 0.5110. Hexadecanoic acid, 2-hydroxy-, methyl ester 36.4 286.251 1.0011. Methyl isostearate 36.7 298.287 0.2812. Methyl oleate 37.5 296.272 8.7013. Methyl lineoleate 37.7 294.256 13.9914. 11,14-Octadecadienoic acid, methyl ester 37.9 294.256 0.6115. Methyl linolenate 38.2 292.24 17.4316. Methyl 9-cis,11-trans-octadecadienoate 40.2 294.256 0.5617. cis-13-Eicosenoic acid, methyl ester 41.9 324.303 0.5518. Methyl arachidate 42.0 326.318 0.6519. Methyl behenate 46.1 354.35 1.4620. Methyl tricosanoate 48.0 368.365 0.4921. Methyl lignocerate 49.9 382.381 1.6022. Methyl 2-hydroxy-tetracosanoate 52.8 398.376 1.6523. Methyl hexacosanoate 53.4 410.412 0.6624. Methyl montanate 57.3 438.444 0.6625. Stigmasta-3,5-diene 58.9 396.376 0.83Saturated Fatty acids                                                                                                        35 %Unsaturated fatty acids                                                                                                      46.4 %Unidentified compounds                                                                                                       18.6 %Table 2 Results of GC/MS analysis of unsaponifiable matter of the n-hexane fraction of SO leavesComp. No. Compound Name RT (min) Mol Weight (amu) Peak area (%)1 Dihydroactinolide 26.9 180.115 0.552 Phytone 30.7 268.277 0.833 Palmitic acid 34.2 256.24 11.074 Loliolid 34.8 196.11 1.645 Phytol 37.3 296.308 33.376 Oleic Acid 38.7 282.256 3.247 Linoelaidic acid 39.0 280.24 10.128 Linolenic acid 39.5 278.225 24.799 Nonacos-1-ene 45.4 406.454 0.2210 1-Tetracosene 49.3 406.454 0.5711 Stigmasterol 66.1 412.371 2.5612 gamma-Sitosterol 68.6 414.386 1.79Total hydrocarbons 83 %Sterols 4.35 %Unidentified compounds 12.65 %

Abl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia

https://egrove.olemiss.edu/cgi/viewcontent.cgi?article=1013&context=pharm_annual_posters_2021

Abl Kinase Inhibitors from Egyptian Spinach Leaves in the Treatment of Chronic Myeloid Leukemia

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