Synthetic Progress and Antifungal Potential of Thiophene Chalcone Derivatives: A Review.

Fungal infections constitute a major global health concern, with annual mortality rates exceeding those of tuberculosis and malaria. This troubling situation has been exacerbated by the emergence of multidrug-resistant fungal strains, which have significantly undermined the effectiveness of current treatments. A number of antifungal medicines are now being utilised in clinical practice. Some of these treatments include azoles, polyenes, pyrimidines, and echinocandins. However, the therapeutic efficacy of these drugs is becoming increasingly limited due to the presence of unwanted side effects, drug-drug interactions, and the rapid development of resistant fungal strains. This growing concern underscores the urgent need for novel antifungal drugs that are safer and more effective than those currently available. Chalcone compounds, whether they are natural or synthetic, have demonstrated significant pharmacological potential due to their extensive range of biological activities. This can be mostly related to the presence of the reactive α, β-unsaturated carbonyl group that is characteristic of chalcones. Furthermore, thiophene is an important scaffold in medicinal chemistry owing to its diverse biological applications. This review article is structured into two main parts. The first part provides an overview of the synthesis of thiophene chalcone derivatives using conventional methods via the Claisen-Schmidt condensation reaction, highlighting the reaction conditions, catalysts, solvent systems, time, and reported yields from recent studies. The second part presents a summary of thiophene chalcone derivatives evaluated over the past decade (2015-2025) for their antifungal properties, discussing the assays performed, fungal strains tested, and the overall biological outcomes reported.