Many new polyisoprenylated
benzophenones with a
bicyclo[3.3.1]-nonane-2,4,9-trione core structure have been isolated from plants in the Clusiaceae family, and their potent
biological properties have been the subject of several studies. This review summarizes the
biological activities reported for these secondary metabolites including cytotoxic, antimicrobial,
antioxidant, and anti-inflammatory activities. Our efforts during the past years have foremost been directed towards isolating new polyisoprenylated
benzophenones, as well as understanding the possible target and mechanism of action through which these compounds arrest
cancer cells and inhibit the progression of the cell-cycle. The transcription of genes is affected in
cancer cells treated with polyisoprenylated
benzophenones; the oncogene c-Myb is down-regulated and endoplasmatic stress genes XBP1, ATF4, and DDIT3/CHOP are turned on. Consequently, the expression of iNOS and cell cycle regulators such as
cyclin D and E are reduced. Evidence presented by independent investigators suggests that polyisoprenylated
benzophenones affect the mediators in the Akt/mTOR stress pathway, although the specific target remains to be discovered. In addition,
benzophenones isolated from plants display high
antioxidant capacity and protect cells from oxidative stress and the formation of ROS involved during the inflammatory process. Since
antiviral activity was initially reported for
guttiferone A, potent synthetic analogues have been developed as effective new non-
nucleoside reverse transcriptase inhibitors (NNRTI) to treat
drug resistant HIV-1. In addition,
benzophenones exert antimicrobial effects particularly against MRSA. The structure-activity relationships of polyisoprenylated
benzophenones from natural sources and those of synthetic analogues are included in this review. Absorption, metabolism, and elimination of
benzophenones are also discussed.