Three-Dimensional (3D) pharmacophore-based identification of possible ATP-synthase inhibitors for mycobacterium tuberculosis (Mtb)
| dc.contributor.author | Fredericks, Ridaa | |
| dc.date.accessioned | 2025-10-03T09:55:58Z | |
| dc.date.available | 2025-10-03T09:55:58Z | |
| dc.date.issued | 2024 | |
| dc.description.abstract | Tuberculosis (TB) is defined as a chronic infectious disease caused by the air-borne transmission of Mycobacterium tuberculosis (Mtb). Due to high prevalence of Mtb in South Africa, it is classified as a high burden country by the World Health Organization (WHO). Multi-drug resistant TB (MDR-TB) strains display a resistance to both Isoniazid and Rifampicin, while extensively drug resistant (XDR-TB) includes resistance to fluoroquinolone as well as other second- line drugs (Capreomycin, Kanamycin and Amikacin). Bedaquiline (BDQ) is a diarylquinoline aimed at inhibiting the adenosine triphosphate (ATP) synthase of MDR-TB, thereby targeting the energy metabolism mechanism of Mtb. Drug regimens utilized prior to BDQ have shown low success rates in patients with XDR-TB. The technologies of computer-aided drug discovery (CADD) has proven to be a powerful tool in reducing costs, as well as time, and ensures the efficiency of lead compound identification. CADD can be divided into two categories; structure-based (SB) and ligand-based (LB) drug discovery. The categories are employed are based on the input data; in this study the LB method was employed as the known descriptors were found to inhibit Mtb ATP-synthase. These descriptors (ligands) were then used to generate pharmacophore models of varying quality and features. A pharmacophore model is a set of features that a ligand requires to be recognized by the drug target, Mtb ATP-synthase. | |
| dc.identifier.uri | https://hdl.handle.net/10566/21013 | |
| dc.language.iso | en | |
| dc.publisher | University of the Western Cape | |
| dc.subject | Mycobacterium Tuberculosis | |
| dc.subject | First-line drugs | |
| dc.subject | Virtual Screening | |
| dc.subject | ATP-synthase | |
| dc.subject | Multi-drug Resistance | |
| dc.title | Three-Dimensional (3D) pharmacophore-based identification of possible ATP-synthase inhibitors for mycobacterium tuberculosis (Mtb) | |
| dc.type | Thesis |