Institut Farmaseutikal & Nutraseutikal Malaysia - Tesis

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Synthesis, Biological Activity And Molecular Docking Of Imidazole-Phenazine Derivatives As Potential Inhibitors For Ns2b-Ns3 Dengue Protease
(2024-12)
Khalili, Nur Sarah Dyana
Dengue is a serious mosquito-borne viral infection that poses a significant global health threat, resulting in approximately half a million deaths annually. The ns2b-ns3 protease plays a crucial role in viral replication and maturation. In this study, a series of imidazole-phenazine derivatives were synthesised via condensation of benzaldehyde derivatives and 2,3-diaminophenazine, forming intermediate schiff bases, followed by air oxidation to induce in situ cyclodehydrogenation. Fifteen compounds were successfully synthesised with yields ranging from 15% to 90%. Spectroscopic techniques, including 1d and 2d nmr, ft-ir, and hrms, were used to elucidate their structures. The compounds were screened for biological activity against denv2 ns2b-ns3 protease using an in vitro assay with the fluorogenic substrate boc-gly-arg-arg-amc. Six derivatives (64b, 64e, 64f, 64g, 64k, and 64m) showed better inhibition of dengue protease, with ic50 values between 54.8 μm and 92.7 μm, compared to quercetin (ic50 = 104.8 μm). The nitro derivative, 2-(3-hydroxy-4-nitrophenyl)-1h-imidazo[4,5-b]phenazine (64f), was the most effective, with an ic50 of 54.8 μm. In silico studies using autodock vina further supported the experimental results, revealing better binding affinities for the six active derivatives, with free binding energies ranging from -8.03 to -8.50 kcal/mol, compared to quercetin (-7.20 kcal/mol). These findings suggest that the synthesised compounds hold promise as potential anti-dengue agents.
Mechanism Of Actions Of Bilimbi Fractions And Its Natural Compounds In Stimulating Brown Adipocyte Differentiation
(2024-03)
Fauzi, Farah Binti Md
Averrhoa bilimbi, or bilimbi, is one of the medicinal plants in the ayurvedic medicine system with various pharmacological activities. The bilimbi leaves were mainly reported for their traditional uses in treating hyperglycemia, diabetes, and related disorders. In previous studies, hexane bilimbi fractions have demonstrated promising anti-obesity properties by stimulating brown adipocyte differentiation. Similarly, major natural compounds of the bilimbi fractions, including phytol and squalene, have also been reported to possess browning activity. However, our understanding of this mechanism of action is still limited to date. To that end, this study focused on a series of transcriptional and translational studies to elucidate the mechanism of action of bilimbi fractions and their corresponding natural compounds in stimulating brown adipocyte differentiation. In the present study, hexane bilimbi fractions (f7, f8, and f9) and their natural compounds (phytol and squalene) substantially stimulated brown adipocyte differentiation at 50 μg/ml and 100 μm, respectively, on the cell-based assay. Based on qrt-pcr analysis, treatment with bilimbi fractions, phytol, and squalene significantly induced the brown-adipocyte marker genes of ucp-1, prdm16, and pgc1-α. Correspondingly, a higher protein expression of cidea, the brown-adipocyte-specific protein marker, was exhibited on a translational level via immunofluorescence assay. The treatment led to the co- development of myotubes and brown adipocytes upon gene knockdown of prdm16. Interestingly,
Materials characterization and aiaided defect classification of pad discoloration in semiconductor wafer fabrication
(2025-09-16)
_Izzuddin Iskandar, Norizan
The discoloration of metal bond pads in semiconductor wafer fabrication is a constant problem because it can be caused by a number of things, from harmless native oxide formation and copper wrinkling to severe corrosion, embedded residues, or surface contamination that make wire bonding less reliable. Automated Optical Inspection (AOI) systems can see color changes, but they can't always tell the difference between low-risk and high-risk defects. This means that they might miss important defects or lose yield. This study gets around this problem by combining advanced material characterization with an AI-enhanced AOI classification framework to improve wafer yield without lowering reliability. We collected AOI images from separate diode and IGBT wafers and put them into seven groups based on the types of defects they had: Non-Visible, Pad Residue, Corrosion, Particle, Copper Wrinkling, Pad Deformation, and Scratches. We used optical microscopy, scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDX), and focused ion beam (FIB) cross-sectioning to find out how bad the defects were. Then we used Failure Mode and Effects Analysis (FMEA) to measure how bad they were. We used these FA-derived classifications to teach a ResNet-18 convolutional neural network (CNN) model on the carefully chosen AOI dataset. The trained AI model was 98.5% accurate overall, 94.8% accurate at selective inking, and had a 0.07% chance of an escapee. Grad-CAM visualizations showed that the network always focused on the right defect features, making it strong against changes in image brightness, contrast, and surface texture. The AI-powered classification system increased wafer yield from 65% to 85%, cut down on false positives, and kept strict detection of high-risk defects. This study shows that combining FA-based defect knowledge with AI-enhanced AOI makes it possible to tell the difference between cosmetic and critical pad discoloration in real time and on a large scale. This is a solution for semiconductor quality control that balances yield optimization with reliability assurance and sets the stage for more AI use in high-volume wafer manufacturing.
Investigation on mechanical and physical properties: a study on vickers hardness, density, and porosity of alumina through the addition of tungsten trioxide
(2025-09-17)
Ibrahim, Maina
Alumina (Al2O3) cutting tools are widely used in high-speed machining mainly because of their intrinsic properties, high hardness, high melting point, and wear resistance; however, the cutting tool often fails when encountering hard material due to its inherent brittleness. Tungsten trioxide (WO₃) is a dense, thermally stable oxide that serves as a hard dispersoid and effective sintering aid in Al₂O₃ matrices. The influence of WO3 addition (0-1 wt.%), on the microstructure, phase formation, and mechanical properties of alumina (Al2O3) was investigated. The Design of Experiment (DOE) is utilized through Response Surface Methodology (RSM), including Central Composite Design (CCD), to optimize two variables among WO3 additions and sintering heating rate. The sintering temperature is fixed at 1600 ℃. The study was designed with target values of approximately 3.9 g/cm³ density, 1600 HV hardness, and porosity below 1%, which are desirable for high-performance Al₂O₃ ceramics. The optimized variables resulted in achieving the desired responses for the hardness, density, and porosity of Al2O3 ceramics. Empirical models are found for responses, and their quality is checked using Analysis of Variance (ANOVA) and other parameters. The microstructure, phase formation, density, and hardness properties were characterized through a field emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Archimedes' principle, and Vickers indentation technique, respectively. Although the incorporation of WO3 into the alumina matrix was intended to improve the composite’s mechanical and physical properties, the experimental results revealed a decrease in hardness and density, from 1386.7HV at 0 wt.% to 415.2 HV at 1.0 wt.%, and density from 3.83g/cm3 to 3.01g/cm3, accompanied by an increase in porosity from 0.26 to 18.21. This suggests that the addition of WO3 may have disrupted particle packing efficiency and hindered densification during sintering, leading to weaker interparticle bonding and a less compact microstructure.
Computational Design And Synthesis Of Potential Ns2b-Ns3 Dengue Protease Inhibitors
(2024-06)
Salin, Nurul Hanim
DENV2, the type of dengue virus commonly found in Southeast Asia, is a major public health concern. In week 6 of 2024, Malaysia reported with 3,631 dengue cases and 10 deaths due to DENV2, marking a 68.75 % increase from the same period in 2023, as reported by the World Health Organization (WHO). Despite the high number of cases, there is currently no clinically proven drug available to inhibit the virus replication, primarily due to the limited availability of 3D crystal structures of targetable protein-protein interactions for drug activation, including the NS2B-NS3 protease from DENV2 and West Nile virus (WNV). To address this issue, docking and pharmacophore modelling have been used with the ligands from DENV2 NS2B-NS3 protease and West Nile Virus. The Systematic Literature Review (SLR) analysis identified 9 active compounds from 2 types of in vitro DENV NS2B-NS3 protease assays i.e. 21 compound classes from cell-free-based assays and 9 compound classes from cell-based assays. 2 of the 9 scaffolds' molecules were identified as the best pharmacophore model based on their high Area Under the Curve (AUC) and Enrichment Factor (EF) values, which were close to 1 and 100% respectively, and were further used as a model for pharmacophore validation.

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