Theses (MSc. Molecular Medicine)

INTRODUCTION: Quebrachitol, an optically active cyclitol derived from plants, has attracted interest as a possible natural product inspiration for pharmaceuticals due to its potential medicinal therapeutic qualities in diabetes, cancer, and drug production. However, the antimicrobial properties of quebrachitol were indefinite. This is the first systematic review to specifically determine, appraise, and consolidate the antimicrobial effects of quebrachitol. METHODS: A comprehensive database search from PubMed, Scopus, and Google Scholar from January 2000 to February 2024 was conducted. All English, full-text, original articles involving experimental, in vivo, or in vitro research were included. Data pertaining to quebrachitol’s effectiveness (nil, partial, or total inhibition) against microorganisms was extracted. In the presence of antimicrobial effects, the minimum effective dosage or duration and mechanism of action were determined. The quality assessments of the articles were performed with QUIN (in vitro) and SYRCLE RoB (in vivo). RESULTS: The research yielded 866 studies, but only 11 met the inclusion criteria, comprising 7 in vitro, 1 in vivo, 1 in ovo, and 2 papers, which combined both in vitro and in vivo trials. Quebrachitol was found to have an anti-infectious effect against Salmonella sp., Candida albicans, infectious bursal disease virus, Newcastle disease virus, and Plasmodium sp. Additionally, there was significant evidence of inhibitions against biofilm in Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA). QUIN tool revealed that 60% of in vitro studies had a low risk of bias, with overall scores ranging from 56.25 to 87.5%. SYRCLE, however, showed that none of the studies contained more than 50% of the studies exhibited low-risk bias. The allocation sequence demonstrated high-risk bias due to a lack of random sequence generation and reliance on non-random approaches like availability or predetermined rules. CONCLUSION: Quebrachitol had demonstrated significant and promising antimicrobial potential in the in vitro studies, showing efficacy against pathogens associated with typhoid, malaria, avian flu disease, and biofilm-related diseases. However, the in vivo findings were inconclusive due to high-risk bias. Thus, further well-designed in vivo research is required to establish the antimicrobial efficacy and safety of quebrachitol and to assess its potential role in developing alternative treatments to address current antimicrobial resistance and pharmacovigilance concerns. Keywords: Quebrachitol, antimicrobial, antibacterial, antifungal, antiviral, antiparasitic, antibiofilm

Propionibacterium acnes (P. acnes), plays a key role in acne pathogenesis by inducing the innate immune system cells to produce certain pro-inflammatory mediators which contribute to the formation of inflammatory acne lesion. The present study was conducted to evaluate the potential of Doani sidr honey and honey polysaccharide rich fraction and madecassoside for antimicrobial and anti-inflammatory activity against P. acnes. The broth dilution method was used to assess the antibacterial activity and the ultrastructural changes in cell morphology before and after exposure to tested samples were studied using transmission electron microscopy (TEM). The tested samples were further investigated for the suppression of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interleukin 8 (IL-8) by testing the supernatants in the co-culture of the human peripheral blood mononuclear cells (PBMCs) and heat killed P. acnes using enzyme immunoassay kits (ELISA). The statistical analysis was done using the Graph Pad Prism 5 program. The Doani sidr honey and its polysaccharide rich fraction were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18%(w/v) and 29 %(w/v) respectively and also the release of TNF-α and IL-8 pro-inflammatory cytokines by suppressing them by more than 90%. TEM micrographs revealed the lethal effects of Doani sidr honey against P. acnes .However, no significant inhibition of the P. acnes growth and the secretion of TNF-α and IL-8 was detected for madecassoside at its highest tested concentration. Our results suggested that Doani sidr honey possess both antimicrobial and anti-inflammatory effects against P. acnes and could possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesise the fraction prepared from Doani sidr honey might contribute to honey activity. Therefore, this fraction needs to be further explored and characterised to find the main contributing phytochemicals and the antibacterial and anti-inflammatory properties in this fraction.

The global crisis of antimicrobial resistance increases the demand for a potent antimicrobial agent. In the search for a novel class of antimicrobial agent, benzothiazole analogue has captured considerable attention as they proved to be promising drugs due to their outstanding antimicrobial activity against bacteria. In this study, a series of benzothiazole analogues (C1-C6) were synthesized and characterized by LC- MS, ATR FT-IR, and proton and carbon NMR spectroscopic techniques. All the synthesized compounds were examined for their in vitro antimicrobial activity against two types of bacterial strains: susceptible strains (Staphylococcus aureus ATCC 35923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Acinetobacter baumannii ATCC 19606) and resistant strains (Methicillin-resistant Staphylococcus aureus ATCC 43300, Pseudomonas aeruginosa ATCC BAA-2108, Escherichia coli ATCC BAA-196, Acinetobacter baumannii ATCC BAA-1797) using broth microdilution method and compared with drug-free control. The antimicrobial activities of the synthesised compounds were expressed as the minimum concentration (MIC) in μM and performed screening at a maximum concentration of 128 μM. Based on the report, all the synthesized compounds (C1-C6) displayed the highest concentration (MIC >128 μM) indicating poor antimicrobial activity against all eight bacterial strains. Therefore, it was concluded that the benzenesulfonylurea derivatisation on the benzothiazole ring system is unfavourable for the antibacterial properties. Keywords: Benzothiazole, in-vitro antimicrobial activity, MIC, microdilution