cucurbitacins

Cucurbitacins are a diverse group of highly oxygenated triterpenoid natural products belonging to the cucurbitane family. They are produced by plants in the Cucurbitaceae such as cucumber, squash, pumpkins, and gourds, where they function mainly as bitter deterrents against herbivores. Chemically, cucurbitacins feature a tetracyclic cucurbitane skeleton with multiple oxygen-containing substituents, and many occur as glycosides, carrying sugar moieties that affect solubility and tissue localization.

Over a dozen cucurbitacins have been described, commonly designated Cucurbitacins A, B, C, D, E and related compounds. Their distribution varies by species, cultivar, developmental stage, and environmental conditions, with bitter varieties showing higher levels. The compounds may accumulate in fruits, seeds, or roots depending on taxon and developmental context.

Biosynthesis begins with the mevalonate pathway, producing isoprenoid units that are assembled to squalene and converted to oxidosqualene. Cyclization by cucurbitadienol synthase yields the cucurbitadienol skeleton, which is then oxidized and rearranged by cytochrome P450 enzymes and other oxidases to generate the diverse cucurbitacins; many also exist as glycosides formed by sugar-transferases.

Biological activity is dominated by bitterness and cytotoxicity. Cucurbitacins deter herbivory and show notable anticancer activity in laboratory studies, but their high toxicity limits therapeutic use in humans. They are commonly studied as chemotaxonomic markers in Cucurbitaceae and as models for structure–activity relationships.