Cancer, particularly in the malignant form, is one of the leading causes of death, and accounts for about 13% of all deaths in the world. Although numerous chemotherapeutic approaches are available today, many of them possess narrow therapeutic indices and may exert severe side effects. In addition, chemotherapy resistance is a major concern in the medical management of many cancer patients. Thus, the discovery and development of new and potent anticancer drugs are urgently needed.
Plants are good sources for the discovery and development of anticancer compounds. Paclitaxel and vinblastine are the prime examples of natural compounds that have been extracted as plant alkaloids for cancers. They both exert strong anti-proliferative actions against various types of cancer cells targeting at microtubule cytoskeleton; however, side effects are often accompanied, occurring in more than 30% of patients. Common side effects include low blood counts, hair loss, diarrhea, peripheral neuropathy, nausea, vomiting, arthralgia, myalgia, low blood pressure, unusual bleeding, fatigue, etc. . . . . Nevertheless, drug resistance remains a major obstacle when using paclitaxel and/or vinblastine or other mainstay anticancer agents to treat malignancies.
Over the past decades, a number of pharmacological studies have been focused on the administration of diterpenes, which are a category of plant-derived compounds composed of two terpene units. Terpenes are indeed a group of aromatic organic unsaturated hydrocarbons based on the general formula (C5H8)n. Diterpenes that contain a kaurane skeleton are referred as a class of diterpenoid compounds possessing a tetracyclic or four-membered ring system. The prefix ent- denotes the configurational inversion at all chirality centers; thus, ent-kaurane is an enantiomer of kaurane. Nevertheless, the ent-kaurane diterpenes are often considered as bioactive components. Till now, hundreds to thousands of ent-kaurane diterpenoids isolated from Isodon species (Lamiaceae) have been intensively investigated due to their wide range of desirable biological activities including cytotoxic, anti-bacterial and anti-inflammatory effects.
It is an objective of the present invention to provide a group of derivatives synthesized based on the ent-kaurane diterpenoid flexicaulin A for treatment of tumors or cancers and the methods to synthesize such diterpenoid derivatives.
Citation or identification of any reference in this section or any other section of this application shall not be construed as an admission that such reference is available as prior art for the present application.
USPTO Backgrounds
USPTO Backgrounds