Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition
Mycobacterium tuberculosis (MTB) remains the leading cause of infection, with a significant fatality rate, owing primarily to drug resistance. MTB contains the enzyme salicylate synthase, which regulates mycobactin production to bind iron ions from the host cell, facilitating the bacteria to grow a...
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| Format: | Article |
| Language: | English |
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Institute for Researches and Community Services Universitas Muhammadiyah Palangkaraya
2024-02-01
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| Series: | Borneo Journal of Pharmacy |
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| Online Access: | https://journal.umpr.ac.id/index.php/bjop/article/view/5513 |
| _version_ | 1797248029131014144 |
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| author | Arfan Arfan Aiyi Asnawi La Ode Aman |
| author_facet | Arfan Arfan Aiyi Asnawi La Ode Aman |
| author_sort | Arfan Arfan |
| collection | DOAJ |
| description |
Mycobacterium tuberculosis (MTB) remains the leading cause of infection, with a significant fatality rate, owing primarily to drug resistance. MTB contains the enzyme salicylate synthase, which regulates mycobactin production to bind iron ions from the host cell, facilitating the bacteria to grow and reproduce. This study focuses on investigating the potential of marine sponge to inhibit the MTB salicylate synthase by exploiting a computational approach combining molecular docking and dynamics simulations. A total of 46 compounds from Xestospongia sp. were chosen from the Marine Natural Products database. The docking results selected four compounds (CMNPD15071, CMNPD7640, CMNPD26706 and CMNPD7639) from this sponge which provides more negative binding energy than their inhibitors (RVE). After reclassifying their interactions, such as hydrophobic and hydrogen bonds, CMNPD15071 (Sulfuric acid mono-(8-methoxy-12b-methyl-6-oxo-2,3,6,12b-tetrahydro-1H-5-oxa-benzo[k]acephenanthrylen-11-yl) ester) and CMNPD7640 (secoadociaquinone B) performed molecular dynamics simulations to assess their stability. These two compounds show a promising stability profile compared to RVE based on RMSD, RMSF, SASA and gyration analysis. Furthermore, the binding affinity prediction of these two compounds using the MM/GBSA calculation method reveals that CMNPD15071 (-38.48 kJ/mol) had the highest affinity for binding to MTB salicylate synthase compared to RVE (-35.36 kJ/mol) and CMNPD7640 (-26.03 kJ/mol). These findings demonstrate that compounds from Xestospongia sp. can block MTB mycobactin biosynthesis by inhibiting salicylate synthase
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| first_indexed | 2024-04-24T20:08:05Z |
| format | Article |
| id | doaj.art-b955dc88255e411e92f61c70775422a9 |
| institution | Directory Open Access Journal |
| issn | 2621-4814 |
| language | English |
| last_indexed | 2024-04-24T20:08:05Z |
| publishDate | 2024-02-01 |
| publisher | Institute for Researches and Community Services Universitas Muhammadiyah Palangkaraya |
| record_format | Article |
| series | Borneo Journal of Pharmacy |
| spelling | doaj.art-b955dc88255e411e92f61c70775422a92024-03-24T03:59:21ZengInstitute for Researches and Community Services Universitas Muhammadiyah PalangkarayaBorneo Journal of Pharmacy2621-48142024-02-017110.33084/bjop.v7i1.5513Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis InhibitionArfan Arfan0Aiyi Asnawi1La Ode Aman2Haluoleo University Universitas Bhakti KencanaState University of Gorontalo Mycobacterium tuberculosis (MTB) remains the leading cause of infection, with a significant fatality rate, owing primarily to drug resistance. MTB contains the enzyme salicylate synthase, which regulates mycobactin production to bind iron ions from the host cell, facilitating the bacteria to grow and reproduce. This study focuses on investigating the potential of marine sponge to inhibit the MTB salicylate synthase by exploiting a computational approach combining molecular docking and dynamics simulations. A total of 46 compounds from Xestospongia sp. were chosen from the Marine Natural Products database. The docking results selected four compounds (CMNPD15071, CMNPD7640, CMNPD26706 and CMNPD7639) from this sponge which provides more negative binding energy than their inhibitors (RVE). After reclassifying their interactions, such as hydrophobic and hydrogen bonds, CMNPD15071 (Sulfuric acid mono-(8-methoxy-12b-methyl-6-oxo-2,3,6,12b-tetrahydro-1H-5-oxa-benzo[k]acephenanthrylen-11-yl) ester) and CMNPD7640 (secoadociaquinone B) performed molecular dynamics simulations to assess their stability. These two compounds show a promising stability profile compared to RVE based on RMSD, RMSF, SASA and gyration analysis. Furthermore, the binding affinity prediction of these two compounds using the MM/GBSA calculation method reveals that CMNPD15071 (-38.48 kJ/mol) had the highest affinity for binding to MTB salicylate synthase compared to RVE (-35.36 kJ/mol) and CMNPD7640 (-26.03 kJ/mol). These findings demonstrate that compounds from Xestospongia sp. can block MTB mycobactin biosynthesis by inhibiting salicylate synthase https://journal.umpr.ac.id/index.php/bjop/article/view/5513DockingMolecular dynamicsMycobacterium tuberculosisMycobactinSalicylate synthaseXestospongia sp. |
| spellingShingle | Arfan Arfan Aiyi Asnawi La Ode Aman Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition Borneo Journal of Pharmacy Docking Molecular dynamics Mycobacterium tuberculosis Mycobactin Salicylate synthase Xestospongia sp. |
| title | Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition |
| title_full | Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition |
| title_fullStr | Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition |
| title_full_unstemmed | Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition |
| title_short | Marine Sponge Xestospongia sp.: A Promising Source for Tuberculosis Drug Development - Computational Insights into Mycobactin Biosynthesis Inhibition |
| title_sort | marine sponge xestospongia sp a promising source for tuberculosis drug development computational insights into mycobactin biosynthesis inhibition |
| topic | Docking Molecular dynamics Mycobacterium tuberculosis Mycobactin Salicylate synthase Xestospongia sp. |
| url | https://journal.umpr.ac.id/index.php/bjop/article/view/5513 |
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