Cucurbitacins as Anticancer Agents: A Patent Review.

BACKGROUND: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its anticancer effects.

OBJECTIVE: This review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and structure-activity relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products.

METHODS: The date about the published patents was downloaded via online open access patent databases.

RESULTS: Cucurbitacins display significant anticancer properties, in particular cucurbitacins B and D which possess very potent effects towards number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C2-OH and C25-OH groups. Most importantly, an acyl ester of the C25-OH and, iso-propyl, n-propyl and ethyl ether groups of the C2-OH demonstrated the most increased anticancer activity.

CONCLUSION: The significant anticancer effects of natural and semi-synthetic cucurbitacins put them as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterdimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.