Nordihydroguaiaretic Acid Analogues: Their Chemical Synthesis and Biological Activities

Nordihydroguaiaretic acid is a natural occurring lignan mainly isolated and commercially produced from desert plant, creosote bush (Larrea divaricata Cav. Or Corillea tridentate), which can be widely found in the border zone of southern of USA and northern of Mexico. During past 100 years, extensive research has demonstrated that nordihydroguaiaretic acid and its synthetic analogues are potentially useful in treating diseases related to cancers, diabetes, viral, bacterial infections, and inflammation. Remarkably, terameprocol, a tetra-O-methyl derivative of nordihydroguaiaretic acid, is currently in Phase I/II clinical trials as an anticancer agent. This review deals with the chemical synthesis and bioactivities of nordihydroguaiaretic acid and its structurally-related derivatives, which possess anticancer, antioxidant, antimicrobial, anti-inflammatory and immunosuppressive activities. The review consists of the data reported in over 100 publications. Keywords: Nordihydroguaiaretic acid, NDGA derivatives, terameprocol, survivin inhibitors, lignan, diarylbutanes, anticancers, anti-HIV