In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i>
This study reports the isolation of three new C<sub>20</sub> diterpenoid alkaloids, Chitralinine A–C (<b>1</b>–<b>3</b>) from the aerial parts of <i>Delphinium chitralense</i>. Their structures were established on the basis of latest spectral technique...
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MDPI AG
2022-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/14/4348 |
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| author | Shujaat Ahmad Manzoor Ahmad Mazen Almehmadi Syed Adnan Ali Shah Farman Ali Khan Nasir Mehmood Khan Asifullah Khan Zainab Mustafa Halawi Hanif Ahmad |
| author_facet | Shujaat Ahmad Manzoor Ahmad Mazen Almehmadi Syed Adnan Ali Shah Farman Ali Khan Nasir Mehmood Khan Asifullah Khan Zainab Mustafa Halawi Hanif Ahmad |
| author_sort | Shujaat Ahmad |
| collection | DOAJ |
| description | This study reports the isolation of three new C<sub>20</sub> diterpenoid alkaloids, Chitralinine A–C (<b>1</b>–<b>3</b>) from the aerial parts of <i>Delphinium chitralense</i>. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (<b>1</b>–<b>3</b>) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC<sub>50</sub> value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol<sup>−1</sup> for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease. |
| first_indexed | 2024-03-09T10:14:41Z |
| format | Article |
| id | doaj.art-b7f03771e5864a8db4fd879c6f2690a4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T10:14:41Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b7f03771e5864a8db4fd879c6f2690a42023-12-01T22:29:19ZengMDPI AGMolecules1420-30492022-07-012714434810.3390/molecules27144348In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i>Shujaat Ahmad0Manzoor Ahmad1Mazen Almehmadi2Syed Adnan Ali Shah3Farman Ali Khan4Nasir Mehmood Khan5Asifullah Khan6Zainab7Mustafa Halawi8Hanif Ahmad9Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal Dir (Upper) 18000, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, University of Malakand, Chakdara Dir (Lower) 18550, Khyber Pakhtunkhwa, PakistanDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaFaculty of Pharmacy, Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam 42300, Selangor, MalaysiaDepartment of Chemistry, Shaheed Benazir Bhutto University, Sheringal Dir (Upper) 18000, Khyber Pakhtunkhwa, PakistanDepartment of Agriculture, Shaheed Benazir Bhutto University, Sheringal Dir (Upper) 18000, Khyber Pakhtunkhwa, PakistanDepartment of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, University of Malakand, Chakdara Dir (Lower) 18550, Khyber Pakhtunkhwa, PakistanDepartment of Medical Laboratory Technology, College of Applied Sciences, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Chemistry, University of Malakand, Chakdara Dir (Lower) 18550, Khyber Pakhtunkhwa, PakistanThis study reports the isolation of three new C<sub>20</sub> diterpenoid alkaloids, Chitralinine A–C (<b>1</b>–<b>3</b>) from the aerial parts of <i>Delphinium chitralense</i>. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (<b>1</b>–<b>3</b>) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC<sub>50</sub> value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol<sup>−1</sup> for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease.https://www.mdpi.com/1420-3049/27/14/4348diterpenoidsX-ray structureacetylcholinesterase (AChE)butyrylcholinesterase (BChE) inhibition<i>Delphinium</i> <i>chitralense</i> |
| spellingShingle | Shujaat Ahmad Manzoor Ahmad Mazen Almehmadi Syed Adnan Ali Shah Farman Ali Khan Nasir Mehmood Khan Asifullah Khan Zainab Mustafa Halawi Hanif Ahmad In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i> Molecules diterpenoids X-ray structure acetylcholinesterase (AChE) butyrylcholinesterase (BChE) inhibition <i>Delphinium</i> <i>chitralense</i> |
| title | In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i> |
| title_full | In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i> |
| title_fullStr | In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i> |
| title_full_unstemmed | In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i> |
| title_short | In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from <i>Delphinium chitralense</i> |
| title_sort | in vitro and in silico investigation of diterpenoid alkaloids isolated from i delphinium chitralense i |
| topic | diterpenoids X-ray structure acetylcholinesterase (AChE) butyrylcholinesterase (BChE) inhibition <i>Delphinium</i> <i>chitralense</i> |
| url | https://www.mdpi.com/1420-3049/27/14/4348 |
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