Synthesis and evaluation of bioluminescent probes as tools for anticancer drug discovery

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2026

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University of Cape Town

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Luciferins are a class of small, light-emitting molecules that produce visible light through an oxidation reaction catalysed by luciferase enzymes. This bioluminescent system, when combined with CCD camera technologies, has enabled groundbreaking advances in measuring mammalian gene expression, protein–protein interactions, biochemical labelling, and small molecule dynamics. Among the luciferins, D-luciferin—originally isolated from the American firefly Photinus pyralis—is the most extensively studied. Synthetic analogues of D-luciferin have become increasingly important due to their incorporation into a wide range of commercially available assay kits, where they serve as sensitive reporters in both in vitro and in vivo applications. This thesis focuses on the development of improved synthetic methods for D-thioluciferin, C6-substituted analogues, and aza-derivatives of D-luciferin, the latter enabling the design of novel caged bioluminescent probes for advanced molecular imaging.
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