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Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking
The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3-O-neohesperidoside (6), isoquercet...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985094/ https://www.ncbi.nlm.nih.gov/pubmed/35424860 http://dx.doi.org/10.1039/d1ra07000b |
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author | Hamed, Ashraf N. E. Abouelela, Mohamed E. El Zowalaty, Ahmed E. Badr, Mohamed M. Abdelkader, Mohamed S. A. |
author_facet | Hamed, Ashraf N. E. Abouelela, Mohamed E. El Zowalaty, Ahmed E. Badr, Mohamed M. Abdelkader, Mohamed S. A. |
author_sort | Hamed, Ashraf N. E. |
collection | PubMed |
description | The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3-O-neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3-O-β-d-glucopyranoside (9). The compounds 2, 3, 5–7 and 9 were isolated for the first time from the genus Carica. An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and clitorin demonstrated the most potent cytotoxic activities with an IC(50) of 1.11 ± 0.06 and 2.47 ± 0.14 μM, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR(wt) kinase inhibition activities with an IC(50) of 37.3 ± 1.9 and 41.08 ± 2.1 nM, respectively, compared with the positive control erlotinib (IC(50) = 35.94 ± 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC(50) of 77.41 ± 4.53 and 92.84 ± 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC(50) = 77.72 ± 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of −4.5287 kcal mol(−1) and RMSD value of 1.69 Å. Clitorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of −14.2074 and RMSD value of 1.56 Å. Compounds (1–3) possessed a good bioavailability score with a 0.55 value. |
format | Online Article Text |
id | pubmed-8985094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-89850942022-04-13 Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking Hamed, Ashraf N. E. Abouelela, Mohamed E. El Zowalaty, Ahmed E. Badr, Mohamed M. Abdelkader, Mohamed S. A. RSC Adv Chemistry The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3-O-neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3-O-β-d-glucopyranoside (9). The compounds 2, 3, 5–7 and 9 were isolated for the first time from the genus Carica. An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and clitorin demonstrated the most potent cytotoxic activities with an IC(50) of 1.11 ± 0.06 and 2.47 ± 0.14 μM, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR(wt) kinase inhibition activities with an IC(50) of 37.3 ± 1.9 and 41.08 ± 2.1 nM, respectively, compared with the positive control erlotinib (IC(50) = 35.94 ± 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC(50) of 77.41 ± 4.53 and 92.84 ± 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC(50) = 77.72 ± 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of −4.5287 kcal mol(−1) and RMSD value of 1.69 Å. Clitorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of −14.2074 and RMSD value of 1.56 Å. Compounds (1–3) possessed a good bioavailability score with a 0.55 value. The Royal Society of Chemistry 2022-03-23 /pmc/articles/PMC8985094/ /pubmed/35424860 http://dx.doi.org/10.1039/d1ra07000b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Hamed, Ashraf N. E. Abouelela, Mohamed E. El Zowalaty, Ahmed E. Badr, Mohamed M. Abdelkader, Mohamed S. A. Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking |
title | Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking |
title_full | Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking |
title_fullStr | Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking |
title_full_unstemmed | Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking |
title_short | Chemical constituents from Carica papaya Linn. leaves as potential cytotoxic, EGFR(wt) and aromatase (CYP19A) inhibitors; a study supported by molecular docking |
title_sort | chemical constituents from carica papaya linn. leaves as potential cytotoxic, egfr(wt) and aromatase (cyp19a) inhibitors; a study supported by molecular docking |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985094/ https://www.ncbi.nlm.nih.gov/pubmed/35424860 http://dx.doi.org/10.1039/d1ra07000b |
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