In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment
Cinnamomum, a genus within the Lauraceae family, has gained global recognition due to its wide-ranging utility. Extensive research has been dedicated to exploring its phytochemical composition and pharmacological effects. Notably, the uniqueness of Cinnamomum lies in its terpenoid content, character...
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Elsevier
2025-06-01
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| Series: | Current Research in Structural Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665928X24000394 |
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| author | Taufik Muhammad Fakih Aden Dhana Rizkita Sintia Ayu Dewi Muchtaridi Muchtaridi |
| author_facet | Taufik Muhammad Fakih Aden Dhana Rizkita Sintia Ayu Dewi Muchtaridi Muchtaridi |
| author_sort | Taufik Muhammad Fakih |
| collection | DOAJ |
| description | Cinnamomum, a genus within the Lauraceae family, has gained global recognition due to its wide-ranging utility. Extensive research has been dedicated to exploring its phytochemical composition and pharmacological effects. Notably, the uniqueness of Cinnamomum lies in its terpenoid content, characterized by distinctive structures and significant biological implications. An intriguing discovery is that sesquiterpene compounds originating from Cinnamomum possess the capacity to function as antagonists for human nicotinic acetylcholine receptors (nAChRs), specifically the nAChRÿ3 subtype, rendering them potential candidates for nicotine replacement therapy (NRT) to aid active smokers. This investigation employed molecular docking and molecular dynamics simulations to assess the inhibitory effects of these compounds on nAChRÿ3. Among the 55 compounds examined, Dihydroxyeudesmene, Gibberodione, and Germacrene-E exhibited the highest binding affinities. These compounds demonstrated robust interactions with the nAChRÿ3 receptor, as evidenced by elevated molecular mechanics general surface area (MM/GBSA) values (ΔG Bind = Dihydroxyeudesmene: −36.45 kcal/mol, Gibberodione: −36.51 kcal/mol, and Germacrene-E: −36.51 kcal/mol). Molecular dynamics simulations further confirmed the stability of these three compounds, indicating their potential to effectively compete with native ligands. However, comprehensive in vitro, in vivo, and clinical investigations are imperative to ascertain the efficacy of these promising therapeutic candidates. |
| format | Article |
| id | doaj-art-7f886ccedf044523a17c17589fd05926 |
| institution | Kabale University |
| issn | 2665-928X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Structural Biology |
| spelling | doaj-art-7f886ccedf044523a17c17589fd059262025-01-04T04:57:01ZengElsevierCurrent Research in Structural Biology2665-928X2025-06-019100162In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatmentTaufik Muhammad Fakih0Aden Dhana Rizkita1Sintia Ayu Dewi2Muchtaridi Muchtaridi3Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia; Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading No.8, Bandung, 40116, IndonesiaDepartment of Pharmacy, Sekolah Tinggi Ilmu Kesehatan (STIKES) Bogor Husada, Jl. Sholeh Iskandar No.4, Bogor, 16164, IndonesiaGraduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, No. 250 Wu-Xing Street, Taipei, 11031, TaiwanDepartment of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia; Research Collaboration Centre for Radiopharmaceuticals Theranostic, National Research and Innovation Agency (BRIN), Jalan Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia; Corresponding author. Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang KM 21, Sumedang, 45363, Indonesia.Cinnamomum, a genus within the Lauraceae family, has gained global recognition due to its wide-ranging utility. Extensive research has been dedicated to exploring its phytochemical composition and pharmacological effects. Notably, the uniqueness of Cinnamomum lies in its terpenoid content, characterized by distinctive structures and significant biological implications. An intriguing discovery is that sesquiterpene compounds originating from Cinnamomum possess the capacity to function as antagonists for human nicotinic acetylcholine receptors (nAChRs), specifically the nAChRÿ3 subtype, rendering them potential candidates for nicotine replacement therapy (NRT) to aid active smokers. This investigation employed molecular docking and molecular dynamics simulations to assess the inhibitory effects of these compounds on nAChRÿ3. Among the 55 compounds examined, Dihydroxyeudesmene, Gibberodione, and Germacrene-E exhibited the highest binding affinities. These compounds demonstrated robust interactions with the nAChRÿ3 receptor, as evidenced by elevated molecular mechanics general surface area (MM/GBSA) values (ΔG Bind = Dihydroxyeudesmene: −36.45 kcal/mol, Gibberodione: −36.51 kcal/mol, and Germacrene-E: −36.51 kcal/mol). Molecular dynamics simulations further confirmed the stability of these three compounds, indicating their potential to effectively compete with native ligands. However, comprehensive in vitro, in vivo, and clinical investigations are imperative to ascertain the efficacy of these promising therapeutic candidates.http://www.sciencedirect.com/science/article/pii/S2665928X24000394Sesquiterpene compoundsCinnamomum genusNicotinic acetylcholine receptors (nAChRs)Inhibitor nAChRÿ3In silico approaches |
| spellingShingle | Taufik Muhammad Fakih Aden Dhana Rizkita Sintia Ayu Dewi Muchtaridi Muchtaridi In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment Current Research in Structural Biology Sesquiterpene compounds Cinnamomum genus Nicotinic acetylcholine receptors (nAChRs) Inhibitor nAChRÿ3 In silico approaches |
| title | In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment |
| title_full | In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment |
| title_fullStr | In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment |
| title_full_unstemmed | In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment |
| title_short | In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment |
| title_sort | in silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors nachrs for nicotine addiction treatment |
| topic | Sesquiterpene compounds Cinnamomum genus Nicotinic acetylcholine receptors (nAChRs) Inhibitor nAChRÿ3 In silico approaches |
| url | http://www.sciencedirect.com/science/article/pii/S2665928X24000394 |
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