Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves
Introduction: Citrus sinensis L. is a candidate plant with promising antimicrobial potential. In the current study, the phytochemical investigation of C. sinensis leaf extract led to the isolation of three coumarins, namely bergapten, xanthotoxin, and citropten. Methods: The chemical structures of t...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024012635 |
| _version_ | 1797304503079272448 |
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| author | Hala Sh Mohammed Mona H. Ibrahim Marwa M. Abdel-Aziz Mosad A. Ghareeb |
| author_facet | Hala Sh Mohammed Mona H. Ibrahim Marwa M. Abdel-Aziz Mosad A. Ghareeb |
| author_sort | Hala Sh Mohammed |
| collection | DOAJ |
| description | Introduction: Citrus sinensis L. is a candidate plant with promising antimicrobial potential. In the current study, the phytochemical investigation of C. sinensis leaf extract led to the isolation of three coumarins, namely bergapten, xanthotoxin, and citropten. Methods: The chemical structures of the isolated coumarins were elucidated using NMR and ESI-MS techniques. The total aqueous ethanol leaf extract and the isolated coumarins were evaluated for their antimicrobial effects against Helicobacter pylori using the MTT-micro-well dilution method and its anti-biofilm activity using MBEC assay, as compared to clarithromycin. Results: The results showed that citropten scored the lowest MIC value at 3.9 μg/mL and completely inhibited the planktonic growth of H. pylori. In addition, it completely suppressed H. pylori biofilm at 31.25 μg/mL. These findings have been supported by molecular docking studies on the active sites of the H. pylori inosine 5′-monophosphate dehydrogenase (HpIMPDH) model and the urease enzyme, showing a strong binding affinity of citropten to HpIMPDH with seven hydrogen bonds and a binding energy of −6.9 kcal/mol. Xanthotoxin and bergapten showed good docking scores, both at −6.5 kcal/mol for HpIMPDH, with each having four hydrogen bondings. Furthermore, xanthotoxin showed many hydrophobic interactions, while bergapten formed one Pi-anion interaction. Concerning docking in the urease enzyme, the compounds showed mild to moderate binding affinities as compared to the ligand. Thus, based on docking results and good binding scores observed with the HpIMPDH active site, an in-vitro HpIMPDH inhibition assay was done for the compounds. Citropten showed the most promising inhibitory activity with an IC50 value of 2.4 μM. Conclusion: The present study demonstrates that C. sinensis L. leaves are a good source for supplying coumarins that can act as naturally effective anti-H. pylori agents. |
| first_indexed | 2024-03-08T00:11:27Z |
| format | Article |
| id | doaj.art-bbab09ca175f4341bd08086b21638464 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T00:11:27Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-bbab09ca175f4341bd08086b216384642024-02-17T06:40:10ZengElsevierHeliyon2405-84402024-02-01103e25232Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leavesHala Sh Mohammed0Mona H. Ibrahim1Marwa M. Abdel-Aziz2Mosad A. Ghareeb3Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11311, EgyptPharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11311, EgyptThe Regional Centre for Mycology and Biotechnology, Al-Azhar University, Cairo, EgyptMedicinal Chemistry Department, Theodor Bilharz Research Institute, Kornaish El-Nile, Warrak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt; Corresponding author.Introduction: Citrus sinensis L. is a candidate plant with promising antimicrobial potential. In the current study, the phytochemical investigation of C. sinensis leaf extract led to the isolation of three coumarins, namely bergapten, xanthotoxin, and citropten. Methods: The chemical structures of the isolated coumarins were elucidated using NMR and ESI-MS techniques. The total aqueous ethanol leaf extract and the isolated coumarins were evaluated for their antimicrobial effects against Helicobacter pylori using the MTT-micro-well dilution method and its anti-biofilm activity using MBEC assay, as compared to clarithromycin. Results: The results showed that citropten scored the lowest MIC value at 3.9 μg/mL and completely inhibited the planktonic growth of H. pylori. In addition, it completely suppressed H. pylori biofilm at 31.25 μg/mL. These findings have been supported by molecular docking studies on the active sites of the H. pylori inosine 5′-monophosphate dehydrogenase (HpIMPDH) model and the urease enzyme, showing a strong binding affinity of citropten to HpIMPDH with seven hydrogen bonds and a binding energy of −6.9 kcal/mol. Xanthotoxin and bergapten showed good docking scores, both at −6.5 kcal/mol for HpIMPDH, with each having four hydrogen bondings. Furthermore, xanthotoxin showed many hydrophobic interactions, while bergapten formed one Pi-anion interaction. Concerning docking in the urease enzyme, the compounds showed mild to moderate binding affinities as compared to the ligand. Thus, based on docking results and good binding scores observed with the HpIMPDH active site, an in-vitro HpIMPDH inhibition assay was done for the compounds. Citropten showed the most promising inhibitory activity with an IC50 value of 2.4 μM. Conclusion: The present study demonstrates that C. sinensis L. leaves are a good source for supplying coumarins that can act as naturally effective anti-H. pylori agents.http://www.sciencedirect.com/science/article/pii/S2405844024012635Citrus sinensisBergaptenXanthotoxinCitroptenHelicobacter pyloriMolecular docking |
| spellingShingle | Hala Sh Mohammed Mona H. Ibrahim Marwa M. Abdel-Aziz Mosad A. Ghareeb Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves Heliyon Citrus sinensis Bergapten Xanthotoxin Citropten Helicobacter pylori Molecular docking |
| title | Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves |
| title_full | Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves |
| title_fullStr | Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves |
| title_full_unstemmed | Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves |
| title_short | Anti-Helicobacter pylori, anti-biofilm activity, and molecular docking study of citropten, bergapten, and its positional isomer isolated from Citrus sinensis L. leaves |
| title_sort | anti helicobacter pylori anti biofilm activity and molecular docking study of citropten bergapten and its positional isomer isolated from citrus sinensis l leaves |
| topic | Citrus sinensis Bergapten Xanthotoxin Citropten Helicobacter pylori Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024012635 |
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