New Quinoline–Urea–Benzothiazole Hybrids as Promising Antitubercular Agents: Synthesis, In Vitro Antitubercular Activity, Cytotoxicity Studies, and In Silico ADME Profiling

dc.contributor.authorMoodley, Rashmika
dc.contributor.authorMashaba, Chakes
dc.contributor.authorRakodi, Goitsemodimo H
dc.contributor.authorNcube, Nomagugu B
dc.contributor.authorMaphoru, Mabuatsela V
dc.contributor.authorBalogun, Mohammed O
dc.contributor.authorJordan, Audrey
dc.contributor.authorWarner, Digby F
dc.contributor.authorKhan, Rene
dc.contributor.authorTukulula, Matshawandile
dc.date.accessioned2022-07-21T12:12:39Z
dc.date.available2022-07-21T12:12:39Z
dc.date.issued2022-05-05
dc.date.updated2022-05-27T13:37:05Z
dc.description.abstractA series of 25 new benzothiazole–urea–quinoline hybrid compounds were synthesized successfully via a three-step synthetic sequence involving an amidation coupling reaction as a critical step. The structures of the synthesized compounds were confirmed by routine spectroscopic tools (1H and 13C NMR and IR) and by mass spectrometry (HRMS). In vitro evaluation of these hybrid compounds for their antitubercular inhibitory activity against the Mycobacterium tuberculosis H37Rv pMSp12::GPF bioreporter strain was undertaken. Of the 25 tested compounds, 17 exhibited promising anti-TB activities of less than 62.5 µM (MIC90). Specifically, 13 compounds (6b, 6g, 6i–j, 6l, 6o–p, 6r–t, and 6x–y) showed promising activity with MIC90 values in the range of 1–10 µM, while compound 6u, being the most active, exhibited sub-micromolar activity (0.968 µM) in the CAS assay. In addition, minimal cytotoxicity against the HepG2 cell line (cell viability above 75%) in 11 of the 17 compounds, at their respective MIC90 concentrations, was observed, with 6u exhibiting 100% cell viability. The hybridization of the quinoline, urea, and benzothiazole scaffolds demonstrated a synergistic relationship because the activities of resultant hybrids were vastly improved compared to the individual entities. In silico ADME predictions showed that the majority of these compounds have drug-like properties and are less likely to potentially cause cardiotoxicity (QPlogHERG > −5). The results obtained in this study indicate that the majority of the synthesized compounds could serve as valuable starting points for future optimizations as new antimycobacterial agentsen_US
dc.identifierdoi: 10.3390/ph15050576
dc.identifier.citationPharmaceuticals 15 (5): 576 (2022)
dc.identifier.citationPharmaceuticals 15 (5): 576 (2022)
dc.identifier.urihttp://hdl.handle.net/11427/36658
dc.language.isoenen_US
dc.publisher.departmentDepartment of Pathologyen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePharmaceuticalsen_US
dc.source.journalissue5en_US
dc.source.journalvolume15en_US
dc.source.pagination576en_US
dc.source.urihttps://www.mdpi.com/journal/pharmaceuticals
dc.titleNew Quinoline–Urea–Benzothiazole Hybrids as Promising Antitubercular Agents: Synthesis, In Vitro Antitubercular Activity, Cytotoxicity Studies, and In Silico ADME Profilingen_US
dc.typeJournal Articleen_US
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