Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses
BackgroundArtemisia absinthium has long been recognized for its therapeutic properties against various diseases. Among these is leishmaniasis, a parasitic infection that remains a global health challenge. Targeting Leishmania N-myristoyltransferase (NMT), a crucial enzyme for parasite survival, repr...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-11-01
|
| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2024.1508603/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850220421115281408 |
|---|---|
| author | Farouk Boudou Amal Belakredar Alaeddine Berkane Ahcen Keziz Huda Alsaeedi David Cornu Mikhael Bechelany Mikhael Bechelany Ahmed Barhoum |
| author_facet | Farouk Boudou Amal Belakredar Alaeddine Berkane Ahcen Keziz Huda Alsaeedi David Cornu Mikhael Bechelany Mikhael Bechelany Ahmed Barhoum |
| author_sort | Farouk Boudou |
| collection | DOAJ |
| description | BackgroundArtemisia absinthium has long been recognized for its therapeutic properties against various diseases. Among these is leishmaniasis, a parasitic infection that remains a global health challenge. Targeting Leishmania N-myristoyltransferase (NMT), a crucial enzyme for parasite survival, represents a promising therapeutic approach. The bioactive compounds in A. absinthium could potentially inhibit NMT and serve as new treatment options for leishmaniasis.AimThis study aims to investigate the phytochemical composition, drug-likeness, and molecular dynamics of A. absinthium bioactive compounds targeting Leishmania NMT, identifying potent inhibitors that could serve as new drug candidates.MethodThe extract of A. absinthium was analyzed using High-Performance Liquid Chromatography (HPLC), identifying nine phenolic compounds, with kaempferol (10.72%) and chlorogenic acid (4.43%) being the most abundant. Drug-likeness and toxicity were evaluated using SwissADME and OSIRIS Property Explorer, focusing on adherence to Lipinski’s rule of five and Ghose’s filter. Molecular docking studies were conducted to evaluate the binding affinity of these compounds to NMT. Molecular dynamics (MD) simulations were performed to assess the stability and flexibility of the NMT-apigenin complex.ResultsMolecular docking identified apigenin as the most potent NMT inhibitor, with a binding energy of −9.6 kcal/mol, forming significant hydrogen bonds with threonine residues 203 and 189. Drug-likeness analysis revealed that most compounds adhered to Lipinski’s rule of five, indicating favorable pharmacokinetic properties. MD simulations confirmed the stability of the NMT-apigenin complex, with root mean square deviation (RMSD) values of 0.04 nm, root mean square fluctuation (RMSF) values between 0.05 and 0.35 nm, and radius of gyration (Rg) values ranging from 2.24 to 2.30 nm. Normal mode analysis further supported the complex’s stability and flexibility.ConclusionThe findings of this study underscore the potential of Artemisia absinthium compounds, particularly apigenin, as promising candidates for the development of new anti-leishmaniasis drugs. The potent inhibition of Leishmania NMT by apigenin, along with its favorable pharmacokinetic and stability profiles, supports its further exploration in antileishmanial drug development. |
| format | Article |
| id | doaj-art-88fc92d846be495fbe91dc6d95146d07 |
| institution | OA Journals |
| issn | 2296-2646 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj-art-88fc92d846be495fbe91dc6d95146d072025-08-20T02:07:05ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462024-11-011210.3389/fchem.2024.15086031508603Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analysesFarouk Boudou0Amal Belakredar1Alaeddine Berkane2Ahcen Keziz3Huda Alsaeedi4David Cornu5Mikhael Bechelany6Mikhael Bechelany7Ahmed Barhoum8Department of Biology, Faculty of Sciences, Djillali Liabes University of Sidi-Bel-Abbes, Sidi-Bel-Abbes, AlgeriaDepartment of Biotechnology, Faculty of Natural Sciences and Life, University of Mostaganem Abdelhamid Ibn Badis, Mostaganem, AlgeriaLaboratory of Chemistry, Synthesis, Properties, and Applications (LCSPA), Department of Chemistry, Faculty of Sciences, Dr. Moulay Tahar University of Saida, Saida, AlgeriaPhysics and Chemistry of Materials Lab, Department of Physics, University of M’sila, M’sila, AlgeriaDepartment of Chemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaInstitut Européen des Membranes, IEM, UMR-5635, University Montpellier, École Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre National de la Recherche Scientifique (CNRS), Montpellier, FranceInstitut Européen des Membranes, IEM, UMR-5635, University Montpellier, École Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre National de la Recherche Scientifique (CNRS), Montpellier, FranceFunctional Materials Group, Gulf University for Science and Technology (GUST), Mubarak Al-Abdullah, KuwaitNanoStruc Research Group, Chemistry Department, Faculty of Science, Helwan University, Cairo, EgyptBackgroundArtemisia absinthium has long been recognized for its therapeutic properties against various diseases. Among these is leishmaniasis, a parasitic infection that remains a global health challenge. Targeting Leishmania N-myristoyltransferase (NMT), a crucial enzyme for parasite survival, represents a promising therapeutic approach. The bioactive compounds in A. absinthium could potentially inhibit NMT and serve as new treatment options for leishmaniasis.AimThis study aims to investigate the phytochemical composition, drug-likeness, and molecular dynamics of A. absinthium bioactive compounds targeting Leishmania NMT, identifying potent inhibitors that could serve as new drug candidates.MethodThe extract of A. absinthium was analyzed using High-Performance Liquid Chromatography (HPLC), identifying nine phenolic compounds, with kaempferol (10.72%) and chlorogenic acid (4.43%) being the most abundant. Drug-likeness and toxicity were evaluated using SwissADME and OSIRIS Property Explorer, focusing on adherence to Lipinski’s rule of five and Ghose’s filter. Molecular docking studies were conducted to evaluate the binding affinity of these compounds to NMT. Molecular dynamics (MD) simulations were performed to assess the stability and flexibility of the NMT-apigenin complex.ResultsMolecular docking identified apigenin as the most potent NMT inhibitor, with a binding energy of −9.6 kcal/mol, forming significant hydrogen bonds with threonine residues 203 and 189. Drug-likeness analysis revealed that most compounds adhered to Lipinski’s rule of five, indicating favorable pharmacokinetic properties. MD simulations confirmed the stability of the NMT-apigenin complex, with root mean square deviation (RMSD) values of 0.04 nm, root mean square fluctuation (RMSF) values between 0.05 and 0.35 nm, and radius of gyration (Rg) values ranging from 2.24 to 2.30 nm. Normal mode analysis further supported the complex’s stability and flexibility.ConclusionThe findings of this study underscore the potential of Artemisia absinthium compounds, particularly apigenin, as promising candidates for the development of new anti-leishmaniasis drugs. The potent inhibition of Leishmania NMT by apigenin, along with its favorable pharmacokinetic and stability profiles, supports its further exploration in antileishmanial drug development.https://www.frontiersin.org/articles/10.3389/fchem.2024.1508603/fullArtemisia absinthiumLeishmaniaN-myristoyltransferasemolecular dockingmolecular dynamics |
| spellingShingle | Farouk Boudou Amal Belakredar Alaeddine Berkane Ahcen Keziz Huda Alsaeedi David Cornu Mikhael Bechelany Mikhael Bechelany Ahmed Barhoum Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses Frontiers in Chemistry Artemisia absinthium Leishmania N-myristoyltransferase molecular docking molecular dynamics |
| title | Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses |
| title_full | Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses |
| title_fullStr | Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses |
| title_full_unstemmed | Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses |
| title_short | Phytochemical profiling and in silico evaluation of Artemisia absinthium compounds targeting Leishmania N-myristoyltransferase: molecular docking, drug-likeness, and toxicity analyses |
| title_sort | phytochemical profiling and in silico evaluation of artemisia absinthium compounds targeting leishmania n myristoyltransferase molecular docking drug likeness and toxicity analyses |
| topic | Artemisia absinthium Leishmania N-myristoyltransferase molecular docking molecular dynamics |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2024.1508603/full |
| work_keys_str_mv | AT faroukboudou phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT amalbelakredar phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT alaeddineberkane phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT ahcenkeziz phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT hudaalsaeedi phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT davidcornu phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT mikhaelbechelany phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT mikhaelbechelany phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses AT ahmedbarhoum phytochemicalprofilingandinsilicoevaluationofartemisiaabsinthiumcompoundstargetingleishmanianmyristoyltransferasemoleculardockingdruglikenessandtoxicityanalyses |