Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation
Leishmaniasis is a group of infectious diseases caused by <i>Leishmania</i> protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the...
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MDPI AG
2023-01-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/1/93 |
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| author | Mohamed A. A. Orabi Mohammed Merae Alshahrani Ahmed M. Sayed Mohamed E. Abouelela Khaled A. Shaaban El-Shaymaa Abdel-Sattar |
| author_facet | Mohamed A. A. Orabi Mohammed Merae Alshahrani Ahmed M. Sayed Mohamed E. Abouelela Khaled A. Shaaban El-Shaymaa Abdel-Sattar |
| author_sort | Mohamed A. A. Orabi |
| collection | DOAJ |
| description | Leishmaniasis is a group of infectious diseases caused by <i>Leishmania</i> protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. <i>Leishmania</i> N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. <i>Withania somnifera</i> leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against <i>Malaria, Trypanosoma</i>, and <i>Leishmania</i> spp. Through a review of previously reported compounds from <i>W. somnifera</i>-afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the <i>Withania</i> genus. These compounds were subjected to molecular docking screening and molecular dynamics against <i>L. major</i> NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to <i>L. major</i> NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity. |
| first_indexed | 2024-03-09T11:42:48Z |
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| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T11:42:48Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-b752c8660590453c80c81a49bf2a23632023-11-30T23:28:54ZengMDPI AGMetabolites2218-19892023-01-011319310.3390/metabo13010093Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics InvestigationMohamed A. A. Orabi0Mohammed Merae Alshahrani1Ahmed M. Sayed2Mohamed E. Abouelela3Khaled A. Shaaban4El-Shaymaa Abdel-Sattar5Department of Pharmacognosy, College of Pharmacy, Najran University, Najran 61441, Saudi ArabiaDepartment of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, Najran 61441, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Nahda University, Beni-Suef 62513, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut-Branch, Assiut 71524, EgyptCenter for Pharmaceutical Research and Innovation, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USADepartment of Medical Microbiology and Immunology, Faculty of Pharmacy, South Valley University, Qena 83523, EgyptLeishmaniasis is a group of infectious diseases caused by <i>Leishmania</i> protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. <i>Leishmania</i> N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. <i>Withania somnifera</i> leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against <i>Malaria, Trypanosoma</i>, and <i>Leishmania</i> spp. Through a review of previously reported compounds from <i>W. somnifera</i>-afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the <i>Withania</i> genus. These compounds were subjected to molecular docking screening and molecular dynamics against <i>L. major</i> NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to <i>L. major</i> NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity.https://www.mdpi.com/2218-1989/13/1/93leishmaniasis<i>L. major</i>N-myristoyltransferasemolecular dockingmolecular dynamics |
| spellingShingle | Mohamed A. A. Orabi Mohammed Merae Alshahrani Ahmed M. Sayed Mohamed E. Abouelela Khaled A. Shaaban El-Shaymaa Abdel-Sattar Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation Metabolites leishmaniasis <i>L. major</i> N-myristoyltransferase molecular docking molecular dynamics |
| title | Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation |
| title_full | Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation |
| title_fullStr | Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation |
| title_full_unstemmed | Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation |
| title_short | Identification of Potential <i>Leishmania</i> N-Myristoyltransferase Inhibitors from <i>Withania somnifera</i> (L.) Dunal: A Molecular Docking and Molecular Dynamics Investigation |
| title_sort | identification of potential i leishmania i n myristoyltransferase inhibitors from i withania somnifera i l dunal a molecular docking and molecular dynamics investigation |
| topic | leishmaniasis <i>L. major</i> N-myristoyltransferase molecular docking molecular dynamics |
| url | https://www.mdpi.com/2218-1989/13/1/93 |
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