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Browsing Laboratory Based Research by Subject "Synthesis and characterisation of betulinic acid derivatives"

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    Synthesis and characterisation of betulinic acid derivatives
    (Kamuzu University of Health Sciences, 2022-05-09) Kumpalume, Peter
    Type and Place of Study: This is an experimental laboratory study that will be conducted at the department of Pharmacy, Kamuzu University of Health Sciences (KUHeS). Problem: Antimicrobial resistance, particularly MDR-TB, remains a major public health threat worldwide. The current MDR-TB medications have been associated with adverse effects and thus, research in new drugs with proven therapeutic effect and safety, is critically important for providing potential solutions for MDR TB. Therefore, we propose to create a new drug entity with increased potency and improved pharmacokinetics properties which will contribute to the fight against antimicrobial resistance. Objectives: The main objective is to investigate the potency of synthesized betulinic acid derivatives against MDR-TB. The specific objectives are four-fold: i) to synthesize new analogues of betulinic acid, ii) to evaluate potency of the derivatives against MDR-TB, iii) to evaluate the stability and solubility of the selected derivatives, and iv) to establish the toxicity profiles of the drug candidate. Methodology: In order to address the objectives, chemical modifications of the identified betulinic acid variant to create new chemical entities will be undertaken. We will explore chemical transformations that involve alkylation, hydroxylation, palladium-catalysed cross coupling and aldol condensation reactions. The synthesized derivatives will be subjected to in vitro anti-TB activity assay using the modified Microplate Alamar Blue Assay (MABA) method. Expected Findings: In this study, we hypothesise that derivatives of betulinic acid will have potency against MDR-TB. It is, therefore, expected that Infrared spectroscopy, Mass spectrometry and NMR spectra of the synthesized chemical entities products will be generated to elucidate their structures. Additionally, in vitro anti-TB activity, pharmacokinetic and cytotoxicity profiles of the products will be determined. Dissemination: The results from this research will be shared with the College of Medicine Research and Ethics Committee (COMREC) and presented at seminars and dissemination workshops at the Kamuzu University of Health Sciences (KUHeS), Ministry of Health and The World Academy of Sciences (TWAS). The results will also be published in peer-reviewed journals.