In silico comparison of antimycobacterial natural products with known antituberculosis drugs
The chemical space based on physicochemical properties and structural features of a diverse group of natural products with reported in vitro activity against different Mycobacterium tuberculosis strains is investigated using in silico tools. This is compared to the chemical space occupied by drugs c...
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| Format: | Article |
| Language: | English |
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American Chemical Society
2022
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| Online Access: | https://doi.org/10.1021/ci300467b http://hdl.handle.net/11408/4928 |
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| author | Espinoza-Moraga, Marlene Njuguna, Nicholas M Mugumbate, Grace Caballero, Julio Chibale, Kelly |
| author_facet | Espinoza-Moraga, Marlene Njuguna, Nicholas M Mugumbate, Grace Caballero, Julio Chibale, Kelly |
| author_sort | Espinoza-Moraga, Marlene |
| collection | DSpace |
| description | The chemical space based on physicochemical properties and structural features of a diverse group of natural products with reported in vitro activity against different Mycobacterium tuberculosis strains is investigated using in silico tools. This is compared to the chemical space occupied by drugs currently recommended for the treatment of various forms of tuberculosis as well as compounds in preclinical and clinical development. Docking studies exploring possible binding affinities and modes of two main clusters of natural products on two different mycobacterial targets are also reported. Our docking results suggest that scytoscalarol, an antibacterial and antifungal guanidine-bearing sesterterpene, can inhibit arabinosyltransferase Mtb EmbC, and the β-carboline alkaloids 8-hydroxymanzamine A and manzamine A can bind to the oxidoreductase of Mtb INHA. On this basis, these products showing high binding affinities to the two targets in silico could be rationally selected for in vitro testing against these targets and/or semisynthetic modification. |
| format | Article |
| id | ir-11408-4928 |
| institution | My University |
| language | English |
| publishDate | 2022 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | ir-11408-49282022-06-28T12:32:34Z In silico comparison of antimycobacterial natural products with known antituberculosis drugs Espinoza-Moraga, Marlene Njuguna, Nicholas M Mugumbate, Grace Caballero, Julio Chibale, Kelly Mycobacterium tuberculosis in silico tools antimycobacterial natural products antituberculosis drugs The chemical space based on physicochemical properties and structural features of a diverse group of natural products with reported in vitro activity against different Mycobacterium tuberculosis strains is investigated using in silico tools. This is compared to the chemical space occupied by drugs currently recommended for the treatment of various forms of tuberculosis as well as compounds in preclinical and clinical development. Docking studies exploring possible binding affinities and modes of two main clusters of natural products on two different mycobacterial targets are also reported. Our docking results suggest that scytoscalarol, an antibacterial and antifungal guanidine-bearing sesterterpene, can inhibit arabinosyltransferase Mtb EmbC, and the β-carboline alkaloids 8-hydroxymanzamine A and manzamine A can bind to the oxidoreductase of Mtb INHA. On this basis, these products showing high binding affinities to the two targets in silico could be rationally selected for in vitro testing against these targets and/or semisynthetic modification. 2022-06-28T12:32:34Z 2022-06-28T12:32:34Z 2013 Article 1549-9596 1549-960X DOI: 10.1021/ci300467b https://doi.org/10.1021/ci300467b http://hdl.handle.net/11408/4928 en Journal of Chemical Information and Modeling;53 (3), 649-660 open American Chemical Society |
| spellingShingle | Mycobacterium tuberculosis in silico tools antimycobacterial natural products antituberculosis drugs Espinoza-Moraga, Marlene Njuguna, Nicholas M Mugumbate, Grace Caballero, Julio Chibale, Kelly In silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| title | In silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| title_full | In silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| title_fullStr | In silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| title_full_unstemmed | In silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| title_short | In silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| title_sort | in silico comparison of antimycobacterial natural products with known antituberculosis drugs |
| topic | Mycobacterium tuberculosis in silico tools antimycobacterial natural products antituberculosis drugs |
| url | https://doi.org/10.1021/ci300467b http://hdl.handle.net/11408/4928 |
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