Valofibrodatans

Valofibrodatans are a family of natural-product–inspired synthetic compounds that feature a polycyclic lactone core with multiple oxygen-containing substituents. They have been investigated as potential antimicrobial and anticancer agents.

Chemically, valofibrodatans A through F share a common polycyclic framework composed of a decalin-like core fused to a lactone-containing ring, with hydroxyl, acetyl, and alkyl groups varying among congeners. The precise configurations and substituents influence bioactivity and physicochemical properties.

Discovery and synthesis: Valofibrodatans were first reported following isolation from marine-derived sources during a natural-products screening program; total syntheses have been achieved for several congeners, enabling structure-activity relationship studies. Biosynthetic origin is attributed to polyketide-like pathways in the producing organisms.

Biological activity: In vitro assays indicate antifungal and cytotoxic activity against several cancer cell lines; selective activity depends on distribution of substituents; proposed mechanisms include disruption of membrane integrity and inhibition of mitochondrial respiration, among others.

Applications and status: Valofibrodatans are viewed as lead scaffolds for medicinal chemistry programs aiming to develop novel antifungal and anticancer agents. They remain at the preclinical stage, with ongoing efforts to optimize potency, selectivity, stability, and pharmacokinetic properties.