Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase
Leishmania species are the causative agents for Leishmaniasis which is one of the neglected tropical diseases causing 70,000 deaths worldwide each year. Squalene synthase enzyme plays a vital role in sterol metabolism which is essential for Leishmania parasite viability. Therefore squalene synthase...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2020-01-01
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| Series: | Experimental Results |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S2516712X20000374/type/journal_article |
| _version_ | 1811156288802914304 |
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| author | Padmika Wadanambi Emanuele Frontoni |
| author_facet | Padmika Wadanambi Emanuele Frontoni |
| author_sort | Padmika Wadanambi |
| collection | DOAJ |
| description | Leishmania species are the causative agents for Leishmaniasis which is one of the neglected tropical diseases causing 70,000 deaths worldwide each year. Squalene synthase enzyme plays a vital role in sterol metabolism which is essential for Leishmania parasite viability. Therefore squalene synthase of Leishmania donovani is a therapeutic target to inhibit growth of parasite. The 3D model of Leishmania donovani Squalene Synthase (LdSQS) was generated by homology modeling and validated through PROCHECK, ERRAT, VERIFY3D and PROSA tools. Virtual screening of the protein was performed by AutoDock with reported inhibitor, E5700 and two natural alkaloids. Molecular interactions were explored to understand the nature of intermolecular bonds between active ligand and the protein binding site residues using UCSF Chimera and PLIP server. The reported inhibitor showed the best binding affinity (-9.75 kcal/mol) closely followed by Ancistrotanzanine B (-9.55 kcal/mol) and Holamine (-8.79 kcal/mol). Ancistrotanzanine B showed low binding energy and permissible ADMET properties. Based on the present study, homology model of LdSQS and Ancistrotanzanine B can be used to design inhibitors with antileishmanial activity. |
| first_indexed | 2024-04-10T04:47:59Z |
| format | Article |
| id | doaj.art-2948d374a60a44c5aa808bf7ba22f6d3 |
| institution | Directory Open Access Journal |
| issn | 2516-712X |
| language | English |
| last_indexed | 2024-04-10T04:47:59Z |
| publishDate | 2020-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Experimental Results |
| spelling | doaj.art-2948d374a60a44c5aa808bf7ba22f6d32023-03-09T12:34:21ZengCambridge University PressExperimental Results2516-712X2020-01-01110.1017/exp.2020.37Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene SynthasePadmika Wadanambi0https://orcid.org/0000-0002-4742-1553Emanuele Frontoni1Department of Parasitology, Faculty of Medicine, University of Colombo, Sri LankaUniversita Politecnica delle Marche, Information Engineerging Department - DII, Ancona, Italy, 60121Leishmania species are the causative agents for Leishmaniasis which is one of the neglected tropical diseases causing 70,000 deaths worldwide each year. Squalene synthase enzyme plays a vital role in sterol metabolism which is essential for Leishmania parasite viability. Therefore squalene synthase of Leishmania donovani is a therapeutic target to inhibit growth of parasite. The 3D model of Leishmania donovani Squalene Synthase (LdSQS) was generated by homology modeling and validated through PROCHECK, ERRAT, VERIFY3D and PROSA tools. Virtual screening of the protein was performed by AutoDock with reported inhibitor, E5700 and two natural alkaloids. Molecular interactions were explored to understand the nature of intermolecular bonds between active ligand and the protein binding site residues using UCSF Chimera and PLIP server. The reported inhibitor showed the best binding affinity (-9.75 kcal/mol) closely followed by Ancistrotanzanine B (-9.55 kcal/mol) and Holamine (-8.79 kcal/mol). Ancistrotanzanine B showed low binding energy and permissible ADMET properties. Based on the present study, homology model of LdSQS and Ancistrotanzanine B can be used to design inhibitors with antileishmanial activity.https://www.cambridge.org/core/product/identifier/S2516712X20000374/type/journal_articleLeishmania donovaniHomology ModelingMolecular DockingLeishmaniasisSqualene Synthase |
| spellingShingle | Padmika Wadanambi Emanuele Frontoni Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase Experimental Results Leishmania donovani Homology Modeling Molecular Docking Leishmaniasis Squalene Synthase |
| title | Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase |
| title_full | Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase |
| title_fullStr | Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase |
| title_full_unstemmed | Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase |
| title_short | Computational approach to identify potential antileishmanial activity of reported inhibitor, E5700 and two natural alkaloids against Leishmania donovani Squalene Synthase |
| title_sort | computational approach to identify potential antileishmanial activity of reported inhibitor e5700 and two natural alkaloids against leishmania donovani squalene synthase |
| topic | Leishmania donovani Homology Modeling Molecular Docking Leishmaniasis Squalene Synthase |
| url | https://www.cambridge.org/core/product/identifier/S2516712X20000374/type/journal_article |
| work_keys_str_mv | AT padmikawadanambi computationalapproachtoidentifypotentialantileishmanialactivityofreportedinhibitore5700andtwonaturalalkaloidsagainstleishmaniadonovanisqualenesynthase AT emanuelefrontoni computationalapproachtoidentifypotentialantileishmanialactivityofreportedinhibitore5700andtwonaturalalkaloidsagainstleishmaniadonovanisqualenesynthase |