Chapter 9 - Jatrophane diterpenes from Euphorbiaceae family

Abstract

Abstract Jatrophane diterpenoids (JDs) have frequently been found existing in plants of Euphorbiaceae family, mainly distributing in Euphorbia genus, such as the famous Traditional Chinese Medicine Gan Sui (E. kansui) and Ze Qi (E. helioscopia). The skeleton of JDs is biosynthesized from four isoprene s by oxidation and cyclization. More than 200 JDs from herbals have been reported so far. This special type of diterpene is characterized by a flexible 5/12-membered carbon ring system substituted with multiple acyl and benzoyl groups. Their significant pharmacological effects have attracted more attention, including the multidrug resistance (MDR) reversal activity, anticancer, antiviral, antimalarial, anti-inflammatory, and lipid-lowering activities. As a good resource of leading compounds, many JD derivatives have been synthesized and modified by organic chemists. MDR remains a major threat for the successful chemotherapy, accounting for approximately 90% of treatment failure. JDs represent a novel scaffold for the discovery and development of effective MDR modulators to be used for cancer treatment in combination with chemotherapy. Among the reported JDs, 138 were examined for their MDR reversal activities and 70% of those were more effective than clinical medicines verapamil and doxorubicin. Based on the characterization of the special natural molecules, some structure-activity relationships (SARs) of related JDs have been concluded. Therefore, we summarized the research progress of JDs and threw light on finding more leading compounds as potential MDR modulators for cancer therapy.