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In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica

The phenanthroindolizidine alkaloid (-)-tylophorine has been reported for its significant anticancer activity working through different biomechanistic pathways. The current study aimed to evaluate the anticancer activity of phenanthroindolizidine alkaloids isolated from Tylophora indica. Six phenant...

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Autores principales: Mostafa, Ehab M., Mohammed, Hamdoon A., Musa, Arafa, Abdelgawad, Mohamed A., Al-Sanea, Mohammad M., Almahmoud, Suliman A., Ghoneim, Mohammed M., Gomaa, Hesham A. M., Rahman, Fatema El-Zahraa S. Abdel, Shalaby, Khaled, Selim, Samy, Khan, Riaz A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144581/
https://www.ncbi.nlm.nih.gov/pubmed/35631719
http://dx.doi.org/10.3390/plants11101295
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author Mostafa, Ehab M.
Mohammed, Hamdoon A.
Musa, Arafa
Abdelgawad, Mohamed A.
Al-Sanea, Mohammad M.
Almahmoud, Suliman A.
Ghoneim, Mohammed M.
Gomaa, Hesham A. M.
Rahman, Fatema El-Zahraa S. Abdel
Shalaby, Khaled
Selim, Samy
Khan, Riaz A.
author_facet Mostafa, Ehab M.
Mohammed, Hamdoon A.
Musa, Arafa
Abdelgawad, Mohamed A.
Al-Sanea, Mohammad M.
Almahmoud, Suliman A.
Ghoneim, Mohammed M.
Gomaa, Hesham A. M.
Rahman, Fatema El-Zahraa S. Abdel
Shalaby, Khaled
Selim, Samy
Khan, Riaz A.
author_sort Mostafa, Ehab M.
collection PubMed
description The phenanthroindolizidine alkaloid (-)-tylophorine has been reported for its significant anticancer activity working through different biomechanistic pathways. The current study aimed to evaluate the anticancer activity of phenanthroindolizidine alkaloids isolated from Tylophora indica. Six phenanthroindolizidine alkaloid (compounds 1–6) in addition to septicine (7), chlorogenic acid (8), and chlorogenic acid methyl ester (9) were isolated from Tylophora indica using different chromatographic techniques including vacuum liquid chromatography (VLC) and preparative high performance liquid chromatography (HPLC). The isolated compounds structures’ were determined using various spectro-analytical techniques, i.e., (1)H-NMR, (13)C-NMR, and mass spectrometry. The isolates’ structural stereochemistry and structural geometries were determined with the help of chiroptical techniques together with comparisons with the available standard samples. The in vitro anti-proliferative activity on three different cell lines, MCF-7, HepG2, and HCT-116 were evaluated. Among all the isolated compounds, tylophorinidine (5) was the most active cytotoxic agent with the lowest IC(50) values at 6.45, 4.77, and 20.08 μM against MCF-7, HepG2, and HCT-116 cell lines, respectively. The bioactivities were also validated by the in vitro kinase receptors inhibition assay. Compound (5) also exhibited the highest activity with lowest IC(50) values (0.6 and 1.3 μM against the Aurora-A and Aurora-B enzymes, respectively), as compared with all the isolated alkaloidal products. The structure activity relationship on the molecular properties, molecular attributes, and bioactivity levels were analyzed, interrelated, and the molecular docking studies on two different receptors, Aurora-A and Aurora-B, were determined, which provided the confirmations of the bioactivity with receptor-ligand geometric disposition, energy requirements, lipophilicity, and detailed the binding pharmacophore involvements responsible for bioactivity elicitations.
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spelling pubmed-91445812022-05-29 In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica Mostafa, Ehab M. Mohammed, Hamdoon A. Musa, Arafa Abdelgawad, Mohamed A. Al-Sanea, Mohammad M. Almahmoud, Suliman A. Ghoneim, Mohammed M. Gomaa, Hesham A. M. Rahman, Fatema El-Zahraa S. Abdel Shalaby, Khaled Selim, Samy Khan, Riaz A. Plants (Basel) Article The phenanthroindolizidine alkaloid (-)-tylophorine has been reported for its significant anticancer activity working through different biomechanistic pathways. The current study aimed to evaluate the anticancer activity of phenanthroindolizidine alkaloids isolated from Tylophora indica. Six phenanthroindolizidine alkaloid (compounds 1–6) in addition to septicine (7), chlorogenic acid (8), and chlorogenic acid methyl ester (9) were isolated from Tylophora indica using different chromatographic techniques including vacuum liquid chromatography (VLC) and preparative high performance liquid chromatography (HPLC). The isolated compounds structures’ were determined using various spectro-analytical techniques, i.e., (1)H-NMR, (13)C-NMR, and mass spectrometry. The isolates’ structural stereochemistry and structural geometries were determined with the help of chiroptical techniques together with comparisons with the available standard samples. The in vitro anti-proliferative activity on three different cell lines, MCF-7, HepG2, and HCT-116 were evaluated. Among all the isolated compounds, tylophorinidine (5) was the most active cytotoxic agent with the lowest IC(50) values at 6.45, 4.77, and 20.08 μM against MCF-7, HepG2, and HCT-116 cell lines, respectively. The bioactivities were also validated by the in vitro kinase receptors inhibition assay. Compound (5) also exhibited the highest activity with lowest IC(50) values (0.6 and 1.3 μM against the Aurora-A and Aurora-B enzymes, respectively), as compared with all the isolated alkaloidal products. The structure activity relationship on the molecular properties, molecular attributes, and bioactivity levels were analyzed, interrelated, and the molecular docking studies on two different receptors, Aurora-A and Aurora-B, were determined, which provided the confirmations of the bioactivity with receptor-ligand geometric disposition, energy requirements, lipophilicity, and detailed the binding pharmacophore involvements responsible for bioactivity elicitations. MDPI 2022-05-12 /pmc/articles/PMC9144581/ /pubmed/35631719 http://dx.doi.org/10.3390/plants11101295 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mostafa, Ehab M.
Mohammed, Hamdoon A.
Musa, Arafa
Abdelgawad, Mohamed A.
Al-Sanea, Mohammad M.
Almahmoud, Suliman A.
Ghoneim, Mohammed M.
Gomaa, Hesham A. M.
Rahman, Fatema El-Zahraa S. Abdel
Shalaby, Khaled
Selim, Samy
Khan, Riaz A.
In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
title In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
title_full In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
title_fullStr In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
title_full_unstemmed In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
title_short In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from Tylophora indica
title_sort in vitro anti-proliferative, and kinase inhibitory activity of phenanthroindolizidine alkaloids isolated from tylophora indica
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144581/
https://www.ncbi.nlm.nih.gov/pubmed/35631719
http://dx.doi.org/10.3390/plants11101295
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