Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities
The present study investigated the neuroprotective potential of the <i>Murraya</i> carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T)...
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2025-07-01
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| author | Himadri Sharma Niti Sharma Seong Soo A. An |
| author_facet | Himadri Sharma Niti Sharma Seong Soo A. An |
| author_sort | Himadri Sharma |
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| description | The present study investigated the neuroprotective potential of the <i>Murraya</i> carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC<sub>50</sub> ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight <i>Murraya</i> carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-e820ac3916e24593a55973b83738df6c2025-08-20T03:36:36ZengMDPI AGMolecules1420-30492025-07-013015313810.3390/molecules30153138Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ ActivitiesHimadri Sharma0Niti Sharma1Seong Soo A. An2Department of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of KoreaDepartment of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of KoreaDepartment of Bionano Technology, Gachon Bionano Research Institute, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 461-701, Gyeonggi-do, Republic of KoreaThe present study investigated the neuroprotective potential of the <i>Murraya</i> carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC<sub>50</sub> ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight <i>Murraya</i> carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents.https://www.mdpi.com/1420-3049/30/15/3138carbazoleneuroprotectionacetylcholinesteraseanti-Aβ fibrilizationmolecular dockingADME/T properties |
| spellingShingle | Himadri Sharma Niti Sharma Seong Soo A. An Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities Molecules carbazole neuroprotection acetylcholinesterase anti-Aβ fibrilization molecular docking ADME/T properties |
| title | Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities |
| title_full | Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities |
| title_fullStr | Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities |
| title_full_unstemmed | Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities |
| title_short | Neuroprotective Evaluation of <i>Murraya</i> Carbazoles: In Vitro and Docking Insights into Their Anti-AChE and Anti-Aβ Activities |
| title_sort | neuroprotective evaluation of i murraya i carbazoles in vitro and docking insights into their anti ache and anti aβ activities |
| topic | carbazole neuroprotection acetylcholinesterase anti-Aβ fibrilization molecular docking ADME/T properties |
| url | https://www.mdpi.com/1420-3049/30/15/3138 |
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