Anticancer agents based on cyclopentenones

Current anti-cancer therapeutics suffer from the problems of low cytotoxic activity for cancer cells, specific cytotoxic activity for specific cancer types, drug resistance after some period as, for example, following therapy with cis-platin, and/or lack of ability to prevent cancers addicted to continuous high-level protein synthesis. We have synthesized 2 chemical compounds that address these therapeutic bottlenecks. The invention relates to 2 novel cyclopentenone derivatives with potent anti-cancer activity. The compounds markedly inhibit the proliferation and induce the killing of cancer cell lines in culture and in animal models. Cells that are resistant to the chemotherapeutic agent cis-platin do not confer cross-resistance to the cyclopentenone derivatives, suggesting that they could provide new therapeutic options in platinum-resistant tumors, addressing a major clinical problem. Another aspect of the invention is the synergetic effects of these compounds with proteasomal inhibitors which may be particularly relevant to the clinical management of ovarian cancer and multiple myeloma where these inhibitors are used.