Benzothiazole as a Promising Scaffold for the Development of Antifungal Agents

Abstract: Despite great efforts in the discovery of antifungal drugs in the last two decades, the increasing incidence of infectious diseases from diverse pathogenic fungi threatens public healthcare and medical sector. Particularly, the invasive infection caused by the yeast Candida Albicans in immunocompromised patients has been widely reported with 25-55% of mortality rate. The major concerns faced by the use of current antifungal agents are the development of fungal resistance, side effects, toxicity, narrow spectrum of fungal activity, and constraints in the route of administration. However, among the four known classes of antifungal drugs currently used in therapy against invasive fungal infections, only one novel antifungal class has been approved by the FDA in 2021 for medical use. In addition, two derivatives with the identification of their corresponding novel molecular targets are currently in the last phase of clinical trial. In this context, the discovery of novel compounds with potential antifungal activity needs to be explored urgently in order to address these concerns. Among various heterocycles, benzothiazole presents a privileged scaffold for developing bio-active compounds with a broad spectrum of pharmacological activities. Many derivatives incorporating the benzothiazole core have been reported to display prominent activity against a variety of non-resistant and resistant fungal microorganisms and have been found to be very attractive for the development of novel antifungal agents. Therefore, in this review, the latest advances in the discovery of benzothiazole-containing antifungal agents are summarized with an emphasis on their spectrum of activity and their structure-activity relationship. We hope that this study will provide researchers structural insight into antifungal molecules for the development of the next generation of antifungal drugs.