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Tocotrienols (T3), a subfamily of vitamin E, are gaining recognition for their potent antioxidant, anti-inflammatory, and neuroprotective properties. However, their use in functional foods and medicinal products faces challenges such as low water solubility, instability under environmental conditions, and susceptibility to oxidative degradation. This study aims to address these challenges by using spray drying as an encapsulation technique to convert liquid nano emulsions of T3 into stable, dry powders. The process is guided by the Quality by Design (QbD) methodology, which optimises the spray drying parameters and the selection of wall materials to enhance the stability of nano-T3 powders. The results indicate that the combination of sodium caseinate and fibersol as wall materials effectively encapsulated T3, preserving its chemical integrity during processing. The optimised spray drying conditions produced nano-sized particles with ideal characteristics such as excellent flowability (10.71 ± 1.12%), wettability (93.07 ± 6.01%), low moisture content (1.79 ± 0.02%), particle size (100.42 ± 48.05 nm) and Vitamin E content (579.00 ± 233.39 mg/g). However, stability testing revealed that while the nano-T3 powder retained its chemical stability, moisture absorption over time led to particle aggregation and a decrease in T3 content. This indicates a need for further optimisation to improve moisture resistance and long-term stability. The study highlights the significant impact of wall materials and spray-drying parameters on the properties of nano-T3 powders and provides valuable insights into enhancing their stability and efficacy. Future research should focus on refining the encapsulation matrix and exploring the incorporation of antioxidants to mitigate degradation, thereby improving the stability and functional applications of nano-T3 in pharmaceuticals, nutraceuticals, and functional foods. In conclusion, this study demonstrates the potential of spray-dried nano-T3 as a stable, bioactive ingredient for diverse applications, with room for improvement in moisture resistance to enhance long-term stability.

The emergence and re-emergence of viral pathogens such as SARS-CoV-2, human immunodeficiency virus (HIV-1), hepatitis C virus (HCV), Zika virus (ZIKV), and dengue virus (DENV) continue to pose significant global health challenges. Viral proteases play a central role in viral replication through polyprotein processing and therefore represent attractive targets for antiviral drug development. This dissertation investigates the identification of synthetic viral protease inhibitors using an integrated in silico approach comprising Structure-Based Pharmacophore Modelling (SBPM), virtual screening, molecular docking, and pharmacokinetic prediction. High-resolution crystal structures of five disease-specific viral proteases (PDB IDs: 8HUR, 4WF8, 3SPK, 2FOM, and 5H4I) were analyzed to generate validated structure-based pharmacophore models using the Pharmit platform. These models were applied to virtually screen large compound libraries, including ZINC and MolPort, to identify molecules exhibiting key interaction features within protease active sites. The top-ranked virtual hits were further evaluated through molecular docking simulations using iGEMDOCK to predict binding conformations, interaction profiles, and relative binding affinities. Drug-likeness and ADMET properties were assessed using the SwissADME web tool. Several chemically diverse lead scaffolds, including triazine, indazole, and isoquinoline cores, demonstrated favorable hydrogen bonding, π–π stacking, and hydrophobic interactions with conserved catalytic residues across multiple viral proteases. Notably, some compounds exhibited multi-target binding potential, indicating suitability for broad-spectrum antiviral development. Overall, this study demonstrates that SBPM integrated with molecular docking provides an efficient and cost-effective computational framework for antiviral lead identification and establishes a strong foundation for future experimental validation and optimization. Keywords: viral proteases; structure-based drug design; pharmacophore modelling; virtual screening

Emerging evidence of meta-analyses suggested that periodontal disease (PD) mediated by oral bacteria may increase the risk of developing neurodegenerative disorders. However, the findings were inconsistent and inconclusive. An umbrella review makes it feasible to summarise the current evidence from the published meta-analyses on this topic and enable the ranking of evidence. In addition, among periodontal pathogens, Porphyromonas gingivalis produces a calcium-independent peptidylarginine deiminase enzyme (PPAD) that induces hypercitrullination, a process that has been proposed to contribute to the onset of neurodegenerative disorders. Nonetheless, PPAD inhibitors have been scarcely reported in the literature, highlighting a significant gap in the current body of research. Therefore, this study aimed to (i) conduct an umbrella review to summarise the associations between oral bacterial diseases and neurodegenerative disorders and assess the credibility of evidence supporting such associations and (ii) evaluate the binding interactions and identify potential inhibitors of PPAD through molecular docking simulations, using the 15 compounds previously identified via 2D ligand-based similarity screening. An umbrella review of 6 eligible meta-analyses including 17 associations was conducted using predefined eligibility criteria and the credibility of evidence was graded according to AMSTAR-2 methodological quality assessment. In parallel, molecular docking simulations were performed to examine binding affinity and key residue interactions of 15 compounds within the PPAD binding site. Nine of 17 associations (52.9 %) showed statistical significance at P ≤ 0.05 based on random-effects models between PD and neurodegenerative disorders. Twelve out of the 17 associations (70.6%) had considerable heterogeneity (I2 > 50%), suggesting that the pooled estimates should be interpreted carefully. Only one association from 17 associations showed a small-study effect. Docking analyses revealed that several compounds exhibited favourable binding affinity within the PPAD binding site interacting with essential residues, particularly (4S)-5-[[(2S)-1-[[(2S)-1-Amino-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-4-benzamido-5-oxopentanoic acid exhibiting binding score of -9.737 kcal/mol. Notably, N-acetyl-L-arginine was estimated to interact directly with His236 of the catalytic triad, suggesting potential inhibition. Collectively, the umbrella review and molecular docking simulations support a biological plausible, though not definitive, link between PD and neurodegenerative disorders. Further longitudinal studies and experimental enzymatic and cellular evaluations are necessary to enhance PPAD-target inhibitor development toward clinical application.

Colorectal Cancer (CRC) is among the foremost causes of cancer-related mortality in Malaysia and worldwide. This warrants the continuous development of novel, efficient and safe therapeutic options. Glucomoringin (GMG) is a secondary metabolite derived from the plant, Moringa oleifera Lam, which is highly known for its nutritional, medicinal and environmental benefits. Preclinical studies have identified promising anticancer properties from extracts of M. oleifera and the associated secondary metabolites. Hence, this study aims to investigate the anticancer potential activity of GMG against human colorectal cancer cell lines (HCT116, HT29, HCC2998 and SW48). The cytotoxic effects of GMG were evaluated through cell viability using the MTT assay at incubation time periods of 24, 48 and 72 hours, with doxorubicin as the standard chemotherapeutic drug. Changes in nuclear morphology and apoptotic features were also assessed through Hoechst 33342 staining and fluorescence microscopy following treatment with GMG. It was observed that GMG manifests a dose-and time-dependent cytotoxicity across all colorectal cancer cell lines, with HCC2998 and SW48 showing the most significant reduction in cell viability, post treatment. GMG-treated cells displayed intensified nuclear fluorescence and irregularity in nuclear morphology, which is consistent with apoptotic cell death features. However, despite reports indicating GMG as a potent anticancer agent, our findings shows that GMG has limited antiproliferative effects, even with an IC50 value of more than 100 μM and prolonged exposure of 72 hours. Additionally, its anticancer activity is also markedly lower compared to that of the standard chemotherapy drug, suggesting limited therapeutic potential in its natural form. Nonetheless, these observations provide significant insights into the limitations of GMG and highlight important future research directions aimed at enhancing and unlocking its therapeutic potential.

Pancreatic cancer (PC) remains a highly lethal malignancy with limited therapeutic options, highlighting the need for alternatives with selective anticancer activity. Syzygium aqueum, a phytochemical-rich tropical plant, exhibits diverse bioactivities, yet its anticancer effects against PC have not been investigated. This study assessed the cytotoxic, antiproliferative, and apoptogenic effects of ten S. aqueum leaf and stem extracts, including hexane, chloroform, ethyl acetate, methanol, and aqueous extracts, on BxPC-3 cells, with selectivity evaluated in non-cancerous 3T3 fibroblasts. Cytotoxicity was assessed by MTT assays at 6.25–200 μg/ml over 24, 48, and 72 hours. Antiproliferative and apoptotic effects were assessed by doubling time analysis and Hoechst 33342 staining, respectively, with all experiments performed in triplicate. At 72 hours, leaf ethyl acetate (LE), stem aqueous (SA), leaf chloroform (LC), and stem ethyl acetate (SE) showed pronounced cytotoxicity, with IC50 values of 49.3, 50.08, 61.23, and 71.80 μg/ml, respectively, and the 72-hour time point was selected for downstream analyses due to consistent IC50 values. Stem hexane (SH) displayed the highest selectivity index exceeding 3, indicating predominantly cancer-specific cytostatic effects. Doubling time analysis demonstrated significant (p < 0.05), dose-dependent proliferation delays for all extracts except leaf aqueous (LA) and LE, whereas Hoechst staining revealed significant increases (p < 0.05) in apoptotic cells across all treatments except SH, which showed minimal apoptosis consistent with its cytostatic profile. Collectively, these findings demonstrate that S. aqueum extracts exhibit promising anticancer activity against PC cells through combined cytotoxic, cytostatic, and pro-apoptotic effects, supporting further mechanistic investigation and therapeutic development.