Bioactive Compounds from Australian Native Medicinal Plants with Distinctive Modifiable and Potentially Useful Chemical Scaffolds

Australian native medicinal plants represent a largely untapped resource for previously undescribed bioactive compounds with unique chemical scaffolds. This review examines recent advances in the identification, characterisation, and therapeutic potential of distinctive modifiable chemical structures from Australian flora, with particular emphasis on compounds that show promise for drug development. Here, the focus is on plants from genera including Terminalia, Eremophila, Eucalyptus, Tasmannia, Kunzea, Eucalyptus, Austrobuxus, and Buchanania, highlighting their ethnopharmacological significance and the structural features that make their bioactive compounds particularly suitable for medicinal chemistry optimisation. Key compound classes discussed include sesquiterpenes, serrulatane diterpenoids, decipiene diterpenoids, meroterpenes, picrotoxane terpenoids, ellagitannins, and flavonoids with unique substitution patterns. This review emphasises structure–activity relationships (SAR), mechanisms of action including efflux pump inhibition and synergistic interactions with conventional antibiotics, and the potential for these scaffolds to effectively address antimicrobial resistance and type 2 diabetes. We identify critical gaps in current knowledge and propose future research directions for translating these distinctive Australian phytochemicals into clinically useful therapeutic agents.