Potential repurposing of four FDA approved compounds with antiplasmodial activity identified through proteome scale computational drug discovery and in vitro assay
- Diallo, Bakary N, Swart, Tarryn, Hoppe, Heinrich C, Tastan Bishop, Özlem, Lobb, Kevin A
- Authors: Diallo, Bakary N , Swart, Tarryn , Hoppe, Heinrich C , Tastan Bishop, Özlem , Lobb, Kevin A
- Date: 2021
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/177531 , vital:42830 , https://doi.org/10.1038/s41598-020-80722-2
- Description: Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein–ligand complexes were finally retained from the 28,656 (36×796) dockings.
- Full Text:
- Date Issued: 2021
- Authors: Diallo, Bakary N , Swart, Tarryn , Hoppe, Heinrich C , Tastan Bishop, Özlem , Lobb, Kevin A
- Date: 2021
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/177531 , vital:42830 , https://doi.org/10.1038/s41598-020-80722-2
- Description: Malaria elimination can benefit from time and cost-efficient approaches for antimalarials such as drug repurposing. In this work, 796 DrugBank compounds were screened against 36 Plasmodium falciparum targets using QuickVina-W. Hits were selected after rescoring using GRaph Interaction Matching (GRIM) and ligand efficiency metrics: surface efficiency index (SEI), binding efficiency index (BEI) and lipophilic efficiency (LipE). They were further evaluated in Molecular dynamics (MD). Twenty-five protein–ligand complexes were finally retained from the 28,656 (36×796) dockings.
- Full Text:
- Date Issued: 2021
Terminaliamide, a new ceramide and other phytoconstituents from the roots of Terminalia mantaly H. Perrier and their biological activities
- Mbosso, Emmanuel, Siwe-Noundou, Xavier, Fannang, Simone V, Song, Achille M, Assob, Jules C N, Hoppe, Heinrich C, Krause, Rui W M
- Authors: Mbosso, Emmanuel , Siwe-Noundou, Xavier , Fannang, Simone V , Song, Achille M , Assob, Jules C N , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191779 , vital:45163 , xlink:href="https://doi.org/10.1080/14786419.2019.1647425"
- Description: Terminaliamide (1), a new ceramide was isolated from the roots of Terminalia mantaly H. Perrier (Combretaceae) along with 4 known compounds (2–5). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy analysis and mass spectrometry. Compound 1 exhibited moderated antibacterial activity towards Staphylococcus aureus with MIC value of 62.5 μg/mL. The crude MeOH extract (TMr) highly reduced Plasmodium falciparum growth with an IC50 value of 10.11 μg/mL, while hexane fraction (F1) highly reduced Trypanosoma brucei brucei growth with an IC50 value of 5.60 µg/mL. All tested samples presented little or no in vitro cytotoxicity on HeLa cell line. The present work confirms that T. mantaly is medicinally important and may be used effectively as an antimicrobial, an antiplasmodial and an antitrypanosomial with promising therapeutic index.
- Full Text:
- Date Issued: 2021
- Authors: Mbosso, Emmanuel , Siwe-Noundou, Xavier , Fannang, Simone V , Song, Achille M , Assob, Jules C N , Hoppe, Heinrich C , Krause, Rui W M
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/191779 , vital:45163 , xlink:href="https://doi.org/10.1080/14786419.2019.1647425"
- Description: Terminaliamide (1), a new ceramide was isolated from the roots of Terminalia mantaly H. Perrier (Combretaceae) along with 4 known compounds (2–5). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy analysis and mass spectrometry. Compound 1 exhibited moderated antibacterial activity towards Staphylococcus aureus with MIC value of 62.5 μg/mL. The crude MeOH extract (TMr) highly reduced Plasmodium falciparum growth with an IC50 value of 10.11 μg/mL, while hexane fraction (F1) highly reduced Trypanosoma brucei brucei growth with an IC50 value of 5.60 µg/mL. All tested samples presented little or no in vitro cytotoxicity on HeLa cell line. The present work confirms that T. mantaly is medicinally important and may be used effectively as an antimicrobial, an antiplasmodial and an antitrypanosomial with promising therapeutic index.
- Full Text:
- Date Issued: 2021
- «
- ‹
- 1
- ›
- »