Kudzanai Ian Tapfuma’s research while affiliated with Stellenbosch University and other places

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Publications (2)

Fig. 1. Cytotoxic effects of 25 Fynbos crude extracts against: (A) MDA_MB 231 TNBC cells at a concentration of 250 mg/mL and cisplatin as a reference drug at 3 mg/mL, (B) Vero cells as normal cell control at a concentration range of 62.5À250 mg/mL and cisplatin at 3 mg/mL. (C) Dose-response curves to determine the IC 50 of the plant crude extracts of (E3), (E9) and (E11) and cisplatin against MDA-MB 231 TNBC cells. (D) IC 50 of the crude leave extracts of (E3), (E9) and (E11) and cisplatin. Cells were cultured in triplicate with the plant crude extract and reference drug cisplatin for 48 h, followed by an MTT viability assay. IC 50 values were calculated using GraphPad Prism 8 software. Data oints denote the mean § standard deviation of triplicate wells.
Fig. 2. Comparison of cell death mechanisms (apoptosis or necrosis) triggered by plant crude extracts I. hamulosa (E3), E. plukenetii (E9) and E. sessiliflora(E11) at 18, 20, and 21 mg/ mL, respectively of treatments and cisplatin (3 mg/mL) relative to untreated controls in MDA-MB 231 TNBC cells elucidated through flow cytometry analysis.
Fig. 4. The effect of caspase activities of triple-negative breast cancer cell line when treated with cisplatin (3 mg/mL) and I. hamulosa (E3), E. plukenetii (E9) and E. sessiliflora (E11) at 18, 20, and 21 mg/mL, respectively for 48 h. (A) Caspases 3 activities of the crude extracts of I. hamulosa, E. plukenetii, E. sessiliflora and cisplatin against triple-negative breast cancer cell line; (B) Caspases 8 activities of the crude extracts of I. hamulosa, E. plukenetii, E. sessiliflora and cisplatin against triple-negative breast cancer cell line; (C) Caspases 9 activities of the extracts of I. hamulosa, E. plukenetii, E. sessiliflora and cisplatin against triple-negative breast cancer cell line; Caspase 3, 8 and 9 activations levels were quantified relative to the control and analysed using GraphPad Prism 8 software. Data represent the mean § standard deviation of three independent experiments, each with technical and biological replicates. Significant differences (**p < 0.001) compared to the untreated control were determined using the two-tailed Student's T-test.
Fig. 5. The influence of glycolysis on MDA-MB 231 TNBC cells following treatment with plant crude extracts (I. hamulosa (E3), E. plukenetii (E9) and E. sessiliflora (E11) at 18, 20, and 21 mg/mL) and cisplatin (3 mg/mL). (A) Basal Glycolysis, (B) Compensatory Glycolysis, (C) Post 2-DG Acidification, and (D) GlycoPER kinetic graph. Quantification of glycolytic impacts was conducted relative to untreated cells and analysed using Agilent Seahorse Analytics and GraphPad Prism 8 software. Data are presented as the mean § standard deviation of two independent experiments, each comprising three technical and two biological replicates. Significant differences (**, * p < 0.001 and 0.05, respectively) compared to the untreated control were determined using the two-tailed Student's T-test.
Fig. 6. The impact of treatment with Cisplatin (3 mg/mL) and plant crude extracts (at their IC 50 concentrations) on the mitochondrial bioenergetics of MDA-MB 231 TNBC cells was evaluated compared to untreated control cells. High-resolution respirometry using the Oroboros Oxygraph-2 K system was used to assess cellular respiration, measured as Flux per Volume, across various stages from routine respiration to complex-IV activity. Triplicate experiments were conducted and mean § SD values were calculated. Statistical analysis was performed using multiple t-tests with the Holm-Sidak method (a = 0.05), incorporating adjusted p-values. Significance levels were indicated as *p < 0.05, **p < 0.001, and ***p < 0.0001.

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Targeting mitochondrial function to inhibit glycolysis and oxidative phosphorylation (OXPHOS) for therapeutic intervention in triple-negative breast cancer line (MDA-MB 231) utilising Cape fynbos
  • Article
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March 2025

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40 Reads

South African Journal of Botany

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Kudzanai Ian Tapfuma

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Kudakwashe Nyambo

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Compound structures of the 12 apoptotic inducer drugs investigated in this study.
Cytotoxicity profile of apoptotic inducer drugs against differentiated THP-1 macrophage cells. The healthy THP-1 macrophages were treated with various concentrations of the drugs corresponding to previously recorded MIC values against M. smegmatis mc²155 and M. tuberculosis H37Rv. Data represents three technical and biological replicates where treated macrophages were analyzed against untreated controls. Data was interpreted as viable percentages and analyzed through ANOVA where p ≤ 0,05*.
Percentage survival of M. smegmatis mc²155 (M.smeg) within THP-1 macrophages relative to untreated control at 6 and 12 h post-treatment with apoptotic inducer drugs. Data is a representative of three biological replicates and shown as mean ± SD. Two-way ANOVA followed by Dunnett’s multiple comparison test was used for data analysis where significant difference is indicated as p ≤ 0.01**, p ≤ 0.001***, p ≤ 0.0001****.
Effect of apoptotic inducer drugs on the secretion of 13 selected cytokines in uninfected and M. smegmatis mc²155-infected THP-1 macrophages. Cytokine expression was evaluated at two time points (6 and 12 h) in infected and uninfected THP-1 cells after treatment with apoptotic inducer drugs. Data was expressed in pg/mL and normalized per column where 0% (purple) was indicated by the lowest value and 100% (red) was indicated by the highest value.
Representative plots showing cytokine changes measured by Luminex multiplex assay in uninfected and M. smegmatis mc²155 infected THP-1 macrophages (A): IL-1β, (B): TNF-α, (C): IL-6. Data were analyzed using two-way ANOVA.

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Repurposing of apoptotic inducer drugs against Mycobacterium tuberculosis

February 2025

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70 Reads

Kudakwashe Nyambo

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Kudzanai Ian Tapfuma

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Computational approaches complement traditional in-vitro or in-vivo assays, significantly accelerating the drug discovery process by increasing the probability of identifying promising lead compounds. In this study, the apoptotic compounds were assessed for antimycobacterial activity and immunomodulatory potential in infected THP-1 macrophage cells. The antimycobacterial activity of the apoptotic compounds was evaluated using the minimum inhibitory concentration (MIC) assay. The immunomodulatory potential of the apoptotic compounds was determined on mycobacterial-infected THP-1 and non-infected THP-1 macrophage cells. The potential binding dynamics of the compounds against InhA were predicted using molecular docking, molecular dynamics, and MM-GBSA binding free energies. The in-vitro MIC assay showed that cepharanthine (CEP) had the highest antimycobacterial activity against Mycobacterium smegmatis mc²155 and Mycobacterium tuberculosis H37Rv, with MICs of 3.1 and 1.5 µg/mL, respectively, followed by CP-31398 dihydrochloride hydrate (DIH) (MICs = 6.2 and 3.1 µg/mL, respectively), marinopyrrole A (MAR) (MICs = 25 and 12.5 µg/mL, respectively), and nutlin-3a (NUT) (MICs = 50 and 25 µg/mL, respectively). MICs for the rest of the drugs were > 200 µg/mL against both M. smegmatis mc²155 and M. tuberculosis H37Rv. Furthermore, the growth of M. smegmatis mc²155 in infected THP-1 macrophage cells treated with DIH, CEP, carboxyatractyloside potassium salt (CAR), and NUT was inhibited by the mentioned drugs. Cytokine profiling showed that DIH optimally regulated the secretion of IL-1β and TNF-α which potentially enhanced the clearance of the intracellular pathogen. Molecular dynamics simulations showed that NUT, MAR, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), and BV02 strongly bind to InhA. However, 17-AAG and BV02 did not show significant activity in-vitro. This study highlights the importance of probing already existing chemical scaffolds as a starting point for discovery of therapeutic agents against M. tuberculosis H37Rv using both pathogen and host directed approaches. The integration of molecular dynamics simulations provides valuable insights into potential scaffold modifications to enhance the affinity.

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