Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora
The stem extract of Uncaria longiflora var. pteropoda (Rubiaceae) has been reported to possess strong α-glucosidase inhibition. However, the specific compounds contributing to this inhibitory potential have not yet been determined. The aim of the present work was to isolate phytochemicals from the m...
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Elsevier
2025-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715624006222 |
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| author | Nurul Aina Suzlin Sulaiman Muhammad Farhan Syakir Nor Azman Mohd Fadhlizil Fasihi Mohd Aluwi Zainul Amiruddin Zakaria Mohammad Jemain Mohammad Ridhwana Fatimah Salim |
| author_facet | Nurul Aina Suzlin Sulaiman Muhammad Farhan Syakir Nor Azman Mohd Fadhlizil Fasihi Mohd Aluwi Zainul Amiruddin Zakaria Mohammad Jemain Mohammad Ridhwana Fatimah Salim |
| author_sort | Nurul Aina Suzlin Sulaiman |
| collection | DOAJ |
| description | The stem extract of Uncaria longiflora var. pteropoda (Rubiaceae) has been reported to possess strong α-glucosidase inhibition. However, the specific compounds contributing to this inhibitory potential have not yet been determined. The aim of the present work was to isolate phytochemicals from the methanolic stem extract of the plant and evaluate the isolated compounds for their antidiabetic potential. Phytochemicals isolation was conducted using various chromatographic methods, with purification achieved through recycling high-performance liquid chromatography (rHPLC) and elucidation performed using various spectroscopic techniques. The antidiabetic potential was evaluated through in vitro α-glucosidase inhibition, kinetics, and molecular docking studies. The crude methanolic extract exhibited α-glucosidase inhibition with IC50 of 138.10 ± 1.32 μg/mL, significantly higher than the previously reported value. Phytochemistry work yielded C-7 diastereomeric pentacyclic oxindole alkaloids (POAs), known as pteropodine and isopteropodine. Kinetics analysis revealed that pteropodine and isopteropodine inhibited α-glucosidase through competitive and noncompetitive mechanisms, with IC50 values of 226.70 ± 2.82 and 98.06 ± 1.98 µg/mL, respectively. Molecular docking and electrostatic potential studies confirmed pteropodine’s interaction with the active sites (Asp349, 1.70 Å and Glu276, 2.94 Å) of α-glucosidase and isopteropodine’s binding to allosteric sites. Although the high concentrations required for effective enzyme inhibition may limit the practical application of these compounds as antidiabetic therapies, this study provides valuable insights into the chemistry underlying the plant’s previously reported antidiabetic potential, particularly in a stereospecific context. The findings further support the unique biological activities attributed to the diastereomeric alkaloids, highlighting their importance in understanding the plant’s therapeutic potential. |
| format | Article |
| id | doaj-art-ccc0f5292ac648d397027af1597f7a4a |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Results in Chemistry |
| spelling | doaj-art-ccc0f5292ac648d397027af1597f7a4a2025-01-29T05:00:35ZengElsevierResults in Chemistry2211-71562025-01-0113101926Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longifloraNurul Aina Suzlin Sulaiman0Muhammad Farhan Syakir Nor Azman1Mohd Fadhlizil Fasihi Mohd Aluwi2Zainul Amiruddin Zakaria3Mohammad Jemain Mohammad Ridhwana4Fatimah Salim5Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, MalaysiaFaculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, MalaysiaUniversiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Persiaran Tun Khalil Yaakob, Gambang, Kuantan, Pahang Darul Makmur, 26300, Malaysia; Centre for Bio-Aromatic Research, Universiti Malaysia Pahang Al-Sultan Abdullah, Lebuhraya Persiaran Tun Khalil Yaakob, Gambang, Kuantan, Pahang Darul Makmur, 26300, MalaysiaBorneo Research on Algesia, Inflammation and Neurodegeneration (BRAIN) Group, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, MalaysiaFaculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, MalaysiaFaculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia; Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Selangor Branch, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Corresponding author.The stem extract of Uncaria longiflora var. pteropoda (Rubiaceae) has been reported to possess strong α-glucosidase inhibition. However, the specific compounds contributing to this inhibitory potential have not yet been determined. The aim of the present work was to isolate phytochemicals from the methanolic stem extract of the plant and evaluate the isolated compounds for their antidiabetic potential. Phytochemicals isolation was conducted using various chromatographic methods, with purification achieved through recycling high-performance liquid chromatography (rHPLC) and elucidation performed using various spectroscopic techniques. The antidiabetic potential was evaluated through in vitro α-glucosidase inhibition, kinetics, and molecular docking studies. The crude methanolic extract exhibited α-glucosidase inhibition with IC50 of 138.10 ± 1.32 μg/mL, significantly higher than the previously reported value. Phytochemistry work yielded C-7 diastereomeric pentacyclic oxindole alkaloids (POAs), known as pteropodine and isopteropodine. Kinetics analysis revealed that pteropodine and isopteropodine inhibited α-glucosidase through competitive and noncompetitive mechanisms, with IC50 values of 226.70 ± 2.82 and 98.06 ± 1.98 µg/mL, respectively. Molecular docking and electrostatic potential studies confirmed pteropodine’s interaction with the active sites (Asp349, 1.70 Å and Glu276, 2.94 Å) of α-glucosidase and isopteropodine’s binding to allosteric sites. Although the high concentrations required for effective enzyme inhibition may limit the practical application of these compounds as antidiabetic therapies, this study provides valuable insights into the chemistry underlying the plant’s previously reported antidiabetic potential, particularly in a stereospecific context. The findings further support the unique biological activities attributed to the diastereomeric alkaloids, highlighting their importance in understanding the plant’s therapeutic potential.http://www.sciencedirect.com/science/article/pii/S2211715624006222UncariaAlkaloidAlpha-glucosidaseMolecular dockingRecycling HPLC |
| spellingShingle | Nurul Aina Suzlin Sulaiman Muhammad Farhan Syakir Nor Azman Mohd Fadhlizil Fasihi Mohd Aluwi Zainul Amiruddin Zakaria Mohammad Jemain Mohammad Ridhwana Fatimah Salim Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora Results in Chemistry Uncaria Alkaloid Alpha-glucosidase Molecular docking Recycling HPLC |
| title | Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora |
| title_full | Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora |
| title_fullStr | Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora |
| title_full_unstemmed | Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora |
| title_short | Stereospecific α-glucosidase inhibition, kinetics, and molecular docking studies on isolated diastereomeric alkaloids from Uncaria longiflora |
| title_sort | stereospecific α glucosidase inhibition kinetics and molecular docking studies on isolated diastereomeric alkaloids from uncaria longiflora |
| topic | Uncaria Alkaloid Alpha-glucosidase Molecular docking Recycling HPLC |
| url | http://www.sciencedirect.com/science/article/pii/S2211715624006222 |
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