https://ir.cut.ac.zw:8080/xmlui/handle/123456789/271 Dissertations & Theses 2026-07-04T11:37:33Z https://ir.cut.ac.zw:8080/xmlui/handle/123456789/817 Discovery of Cucurbita maxima compounds as Schistosoma mansoni and Schistosoma haematobium inhibitors. Mtemeli, Floryn Lynorah Over 200 million people worldwide suffer from schistosomiasis, a disease usually associated with poverty and poor sanitation. A single drug, praziquantel (PZQ), has been used by the medical community since the 1970s. The emerging evidence of resistance of the Schistosoma parasite to praziquantel, and the drug's ineffectiveness against juvenile stages of the parasite, calls for alternative drug. The exploration of the inhibition potential of compounds from Cucurbita maxima using molecular docking studies on Schistosoma mansoni purine nucleoside phosphorylase (SmPNP) and Schistosoma haematobium 28-kDa glutathione S-transferase (Sh28kDaGST) was done. Following molecular docking studies and analysis of the active sites, the primary amino acids that were observed and shown to be involved in the SmPNP-ligand interaction are CYS 33, ARG 86, HIS 88, TYR 90, ALA 118, ALA 119, PRO 200, TYR 202, GLU 203, VAL 219, MET 221, THR 244, ASN 245, PRO 257 and HIS 259. For the Sh28dKa-ligand interaction, the primary amino acids were PHE 11, ARG 16, TRP 41, LEU 53, GLU 70 and SER 71. Momordicoside I aglycone binds to SmPNP HIS88 with the lowest binding energy of -7.9kcal/mol. Balsaminoside B binds to Sh28kDaGST with a binding energy of −7.6kcal/mol by hydrogen bond interaction with TRP 41, LEU 53 and SER 71. The anti-schistosomal activity of C. maxima seeds extract alone and in combination with PZQ on Schistosoma mansoni-infected mice and were also done. The parasites were sampled from the Mupfure River in the Mashonaland East province of Zimbabwe from three different village sites namely Chikanza, Matimure and Mwedziwandira. Infection of guinea pigs with Schistosoma haematobium was attempted. Unfortunately, the infection in the guinea pigs was unsuccessful. Results indicate a statistically significant reduction in granuloma size in the C. maxima extract +praziquantel treated group, with a 13,24% margin compared to the C. maxima seeds extracts treated group. Treatment by C. maxima seeds extract and C. maxima seeds extract + PZQ significantly reduced the egg count in intestines and live (p=0.00; p=0.00 & p=0.00), respectively. There was no significant difference in the effect of the village sites from where the parasites were sampled (p>0.05). The anti-schistosomal effect of C. maxima extracts and their synergistic effects when in combination with praziquantel were observed. In addition to providing a predictive model for interactions between C. maxima ligands, SmPNP and Sh28kDaGST, the in vivo work validated the in silco findings and confirmed that C. maxima does have antischistosomal properties. We propose that as future work, in vitro studies on the target proteins be carried out to elucidate the mechanism of action of the C. maxima plant. We also recommend performing selectivity tests of the best-performing compounds on the target proteins. Overall, our study lays a crucial foundation in the development of a new drug against schistosomiasis and we recommend that C. maxima seeds and their combination with praziquantel be considered as candidates for the development of a new drug against schistosomiasis. 2023-05-01T00:00:00Z https://ir.cut.ac.zw:8080/xmlui/handle/123456789/705 An Internal Audit framework for enhancing management control in Zimbabwean local Governments. Chigutei, Nisha The study looked at how Risk-Based Auditing (RBA) frameworks were used in Zimbabwean local government financial management systems, specifically to improve accountability and performance. The main objective was to investigate how technology-enabled internal auditing improves management control systems in Zimbabwean local governments. The goal of the research was to investigate how technology-enabled internal auditing improves management control systems in Zimbabwean local governments, with a focus on assessing adoption of RBA, evaluating tools like Integrated Financial Management Information Systems (IFMIS), Geographic Information Systems (GIS), continuous auditing, and control self-assessment, and identifying barriers to implementing RBA. The research used a mixed-methods approach underpinned by a pragmatist philosophy, involving a population of local government officials and auditors, with 96 participants selected through stratified and purposive sampling techniques. The study assessed the current state of internal auditing practices, the effectiveness of technological tools like IFMIS, and the barriers to implementing RBA. The major findings revealed that, while RBA was moderately adopted by local governments, substantial obstacles remained, including insufficient resources, inadequate auditor training, and political meddling that hindered the auditing process. Despite these challenges, the study highlighted RBA's potential benefits, including more openness, timely reporting, and more efficient financial management. Finally, the study made actionable recommendations for strengthening internal audit functions through improved training programs, better technological integration, and establishing a supportive governance structure. Furthermore, the relationship between technology-driven audits and management control system performance was discussed, revealing that while technology improves accountability and transparency, its advantages are frequently negated by systemic governance flaws. Quantitative data were analyzed using SPSS. Through addressing these deficiencies, the study hoped to contribute to the enhancement of financial accountability and operational efficiency in Zimbabwe's local government sector, thereby helping the larger goal of effective public service delivery. 2026-01-01T00:00:00Z https://ir.cut.ac.zw:8080/xmlui/handle/123456789/394 Structure-based hit-to-lead design, optimization, and synthesis of tetrahydro-1,3,5-triazine-2-amine derivatives as potential inhibitors of Mycobacterium tuberculosis Dihydrofolate Reductase (MtbDHFR). Zindoga, Albert Among several Mycobacterium tuberculosis potential drug targets, Mycobacterium tuberculosis Dihydrofolate Reductase (MtbDHFR) is a key enzyme involved in folate metabolism. It is an important target in which its inhibition results in mycobacterial cell death. Several successful anti-folates against infectious diseases exist, but none have been developed to combat tuberculosis. Previously, two potent anti-tuberculosis phenotypic hits belonging to the tetrahydro-1,3,5-triazine-2-amine (THT) family, were predicted and confirmed as inhibitors of MtbDHFR. Therefore, optimizing these confirmed hits can lead to a new class of anti-tuberculosis compounds that are target specific and highly potent. The study aims to design and synthesize tetrahydro-1,3,5-triazine-2-amine derivatives as potential anti-TB hit based on the 3D structure of MtbDHFR. Structure-activity relationship (SAR) was applied in the design of 113 tetrahydro-1,3,5-triazine-2-amine based on the 3D structure of MtbDHFR. The rest of the compounds were designed by scaffold hopping via the synergy of Marvin Sketch (manual design) and Spark software program to inflate the library to a capacity of 1700 compounds. By considering the key distinguishing features between human-DHFR and MtbDHFR, the matter of selectivity was well addressed. Resultantly 23 out of 40 tested compounds favored MtbDHFR inhibition over Human DHFR in terms of selectivity. The generated compound library was subjected to virtual screening using Auto-Dock Vina to predict the binding affinities and the best binding pose of each compound inside the binding site of the MtbDHFR target. Next, ADMET studies were then performed to predict the pharmacokinetics and toxicity profiles of the designed compounds. Furthermore, Molecular Dynamics (MD) simulations were done on four ligand complexes where conformational stability, residue flexibility (RMSF), compactness (Rg), and hydrogen bonding were analyzed. The Molecular Dynamics (MD) simulation results support excellent binding affinities of these ligands observed earlier by molecular docking. The study demonstrated a successful hit to lead optimization and all compounds were identified with, binding affinities ranging from -6.5 to -14.1 kcal/mol, improved drug-like, and ADMET properties. Two of the high-ranked compounds were selected for synthesis. The carbodiimide, DCC-mediated coupling reaction was used to synthesize two of the pre-qualified compounds AZ01 and TB1 which had a percentage yield of 74 and 67% respectively, paving the way for further exploration and experimentation work such as biological assays and potentially preclinical testing. Conclusively it is imperative to mention that 1,3,5-triazine scaffolds holds a great promise to the design of novel effective anti-TB leads and may be a beacon of hope for the eradication of this global burdensome TB disease. vi Furthermore, the inter-disciplinary project has advanced basic science at CUT and boosted molecule design and synthesis in addition to encouraging inter-disciplinary collaborations. 2023-03-01T00:00:00Z https://ir.cut.ac.zw:8080/xmlui/handle/123456789/393 Techno-economic analysis and life-cycle assessment of bio-oil production from microwave-assisted pyrolysis of pine sawdust Makepa, Denzel Christopher Pyrolysis is a promising method for producing bio-oil from biomass. However, bio-oil must be upgraded before it can be used as fuel in internal combustion engines. While biofuels are often considered renewable and eco-friendly, it is important to understand the complete economic and environmental impacts of biofuel production to make informed decisions about their use. This study aims to evaluate the process’s economic viability and the environmental sustainability of converting pine sawdust to crude bio-oil via microwave-assisted pyrolysis. The study used ASTM D 410-84, D3173-5 and ASTM D5373 standards to characterize the feedstock and pyrolysis products, and thermogravimetric analysis to study the thermal degradation behavior of pine sawdust. Gas chromatography-mass spectrometry (GC-MS) and Fourier transform-infra red (FTIR) were used to analyze the compositional properties of the organic phase and fatty acid methyl esters. The study found that the optimal operating conditions for producing the highest amount of bio-oil were achieved at 550℃ and 1 atm, yielding 42.28 wt.% of bio-oil, with phenolics contributing the greatest percentage of organic compounds. Transesterification improved the bio-oil properties by converting organic acids and oxygenated compounds to fatty acid methyl esters with a concentration of 510.05 mg/L. The study also evaluated the economic feasibility of the process, establishing the minimum selling price (MSP) of bio-oil, and predicted MSP for biodiesel. The MSP of bio-oil and biodiesel was established through the use of a discounted cashflow rate of return (DCFROR) analysis. The study found that the process was economically viable, with a MSP of $1.14/L of bio-oil and a predicted MSP for biodiesel of $2.31/L. The minimum selling price of biodiesel was consistent with the prices reported in previous studies, albeit with minor variations primarily attributed to variations in feedstock composition and the complexity of the thermochemical conversion process. The life cycle assessment (LCA) utilized a cradle-to-gate system boundary approach. To evaluate the environmental sustainability of the system, the Ecoinvent v3.7 database in openLCA v2.0 software. They conducted an analysis of 18 environmental impact categories using the ReCiPe 2016 (H) midpoint impact assessment methodology. However, the study found that the process had environmental impacts, including global warming potential, photochemical oxidant formation, and human toxicity, primarily due to the use of methanol in the biofuel synthesis stage. The study suggests that implementing sustainable practices, such as using organic fertilizers, optimizing transportation routes, implementing gas cleaning technologies, and effective waste management practices, could enhance the environmental performance of the biofuel production system. 2023-01-01T00:00:00Z