Dillon, M 2020, In vitro screening of Trametes versicolor and Acacia nilotica derivatives for antimalarial efficacy , MRes thesis, University of Salford.
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Abstract
Of the plethora of parasitic diseases that afflict mankind, malaria remains the most prevalent. The disease has caused severe global health problems, putting 3.2 billion people at risk of developing the Plasmodium infection. With current front-line treatments such as the artemisinins showing early warning signs of resistance, new novel drug leads are needed to ensure the safety of the populations at risk. With resistance growing, the development of new antimalarials is still slow as a result of tedious and prolonged discovery pipelines. Traditionally, antimalarial drug discoveries have derived from natural products (e.g. quinine and artemisinin derivatives). New natural product usage has diminished during the past few decades as a result of advances in molecular target detection and high-throughput screening technologies. Technical difficulties associated with the natural product extraction process, further compounded the issues. This study aims to investigate the potential antimalarial activity of Trametes versicolor and Acacia nilotica using solvent extracts in an in vitro study on Plasmodium falciparum (strain K1). Species validation from different collection sites was carried out using comparison of spectra generated with Fourier transform infra-red spectroscopy. To test drug efficiency, the parasites were exposed to the compounds for 48- and 72-hour incubations at trophozoite and ring stage. The specific doses for exposure were concentrations of 12.5 μg/ml, 25 μg/ml, 50 μg/ml, 100 μg/ml and 200 μg/ml, for each extracted compound. MTT assays were performed alongside parasite IC50 studies in order to define the toxicity profiles. 48 hours cycle IC50 values for T. versicolor and A. nilotica ethanol extractions were 45.54 ± 1.12 μg/ml and 45.54 ± 1.12 μg/ml while the 72-hour cycle was 27.47 ± 1.09 μg/ml and 37.3 ± 1.07 μg/ml on the multi-drug resistant strain K1 of Plasmodium falciparum. The methanol extraction on the other hand gave IC50 values of 20.2 ± 1.11 μg/ml after 48 hours cycle and 44.3 ± 1.06 μg/ml after 72 -hours for A. nilotica. The cytotoxicity assay carried out on HepG2 gave IC50 values of 51.6 ± 1.2 μg/ml for T. versicolor and 29.1 ± 1.07 μg/ml for A. nilotica ethanol extract. The cytotoxicity assay indicated a very narrow therapeutic index for both the T. versicolor (TI =1) and A. nilotica (TI = 0.6). However, given the previously published anti-cancer properties for both plant products, the use of the traditional HepG2 model for cytotoxicity is debated. This study confirmed these natural products as potential leads for new novel drug development. The evidence presented justifies further evaluation and validation of T. versicolor and Acacia nilotica as natural product leads for antimalarial drug discovery.
| Item Type: | Thesis (MRes) |
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| Contributors: | Nirmalan, NJ (Supervisor) |
| Schools: | Schools > School of Environment and Life Sciences > Biomedical Research Centre |
| Depositing User: | Mason Dillon |
| Date Deposited: | 21 Apr 2021 14:03 |
| Last Modified: | 27 Aug 2021 21:50 |
| URI: | https://usir.salford.ac.uk/id/eprint/59555 |
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