Description of solution
Cancer is a major cause of death; for example, renal cancer is an important contributor to morbidity and mortality. Current therapies are lacking due to incomplete therapeutic responses and potential adverse side effects, so new therapies are always sought after (Ratanyake et al., Organic Letters 2008, 1 1 , 1, 57-60). Attempts have been made to identify and isolate medicinal products for cancer treatment from plant materials. For example, a large number of Phyllanthus species have been found in tropical and subtropical regions of the world and some have been used in traditional medicines. Englerin A and englerin B have been isolated and purified from the root bark and stem bark of the plant Phyllanthus engleri Pax (Euphorbiaceae). Since then, englerin compounds and derivatives thereof have been studied as potential therapeutics.

The present invention further provides a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier.

The addition of the double bond in the core structure of formula (I) twists the geometry of the core, which might be expected to destroy the therapeutic activity. However it was surprisingly discovered that compounds of formula (I) are therapeutically active, especially against certain cancers, such as renal cancer. This was particularly unexpected, since few modifications of the core sesquiterpene structure have been previously reported, and loss of the five-membered ring or removal of the 4-methyl substituent provides compounds that do not effectively inhibit renal cancer cell growth (Xu et al., Chem. Asian J, 2010, 7, 1052-1060; Dong et al, J. Asian Nat. Prod. Res., 2014, 16, 629-639.). Accordingly, the present invention also provides a method of treating a disease, such as cancer or diabetes, in a mammal in need thereof comprising administering to the mammal an effective amount of the compound.

Collaborators

Fundació Institut Catala d’Investigació Química (ICIQ), Universitat Rovira i Virgili (URV), the United States of America, as represented by the Secretary, Department of Health and Human Services.

Funding

This invention was made with Government support under project number ZIA BC011470 05 funded by the National Institutes of Health, National Cancer Institute (USA). The Government has certain rights in this invention.

License

Patent licensed to the National Institute of Health EEUU (NIH) and the National Cancer Institute (NCI) from USA.