Department of Chemistry and Polymer Science

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Browsing Department of Chemistry and Polymer Science by browse.metadata.advisor "Blackie, Margaret"

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    Design and synthesis of dual-heterocyclic hybrid inhibitors for malaria and cancer
    (Stellenbosch : Stellenbosch University, 2021, 2021-12) Hay, Jonathan Bruce; Blackie, Margaret; Willem, van Otterlo; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: In this study, the design and synthesis of a series of 12 known and novel 2,4-substituted benzofuran and benzothiophene derivatives, 4 known 4-aminoquinolines and 16 novel dual heterocyclic hybrids are described. The series of hybrid compounds was successfully synthesized by amide and ester functional group couplings of benzofuran carboxylic acid derivatives with 4-aminoquinolines, and similarly, benzothiophene carboxylic acids with 4- aminoquinolines. In addition, a short investigation into the synthesis of symmetrical heterocycles successfully produced two novel bis-benzothiophene compounds. These known and novel heterocycle and hybrid compounds were screened in vitro against the chloroquine sensitive NF54 strain of Plasmodium falciparum to evaluate their potential as antiplasmodial agents. The results from the biological screening are presented and discussed for the heterocycles and indicated that the benzofuran and benzothiophene analogues exhibited poor antiplasmodial activity (IC50: >10 μM). In contrast, the entire series of novel dual heterocyclic compounds exhibited good antiplasmodial activity with IC50 values between 0.089 μM and 2.75 μM concentrations, with the four known 4-aminoquinolines showing antiplasmodial activity between 0.090 μM and 5.84 μM concentrations. A small group of hybrids and the two symmetrical compounds were also subjected to preliminary in vitro anticancer screening against WHCO1 oesophageal cancer cells to evaluate whether there was any potential for these types of compounds to be cancer inhibitors. Results obtained from the preliminary screening indicated that there was indeed anticancer activity with IC50 values below 10 μM, however there are still some results outstanding to confirm the initial data. This study has provided results in support of dual heterocyclic hybrid compounds based on benzofuran/quinoline and benzothiophene/quinoline scaffolds, that have the potential to inhibit Plasmodium falciparum and can be viable scaffolds for designing new antimalarial drugs.