Repurposing the antispasmodic drug pinaverium bromide as a novel antifungal agent and synergist against Candida albicans

Fungal infections represent a significant and growing threat to public health, exacerbated by an expanding population of immunocompromised individuals and the increasing prevalence of resistance to conventional Antifungal agents. Drug repurposing offers a strategic and efficient pathway for Antifungal discovery, leveraging existing pharmacotherapies to reduce development costs and mitigate safety risks. This study evaluated the Antifungal potential of pinaverium bromide, an FDA-approved antispasmodic drug for functional gastrointestinal disorders, against the prevalent pathogen Candida albicans. Our in vitro analyses revealed that pinaverium bromide demonstrated standalone Antifungal activity and acted synergistically with amphotericin B or azole drugs. Moreover, it effectively attenuated key virulence factors of C. albicans, including hyphal formation and biofilm development. The therapeutic efficacy of both monotherapy and combination therapy with amphotericin B or voriconazole was validated in two murine models of systemic candidiasis. Mechanistically, pinaverium bromide disrupted mitochondrial function, induced apoptotic cell death, and impaired iron homeostasis in C. albicans. When combined with amphotericin B, it potentiated the drug's effect by amplifying Reactive Oxygen Species accumulation and enhancing membrane permeabilization. These findings support the potential of pinaverium bromide as a novel Antifungal agent, either when used alone or in combination with established Antifungal therapies.