Potential of Cyclopenta[b]benzofurans from Aglaia Species in Cancer Chemotherapy

Soyoung      Kim; Angela   A.   Salim; Steven   M.   Swanson; A.      Douglas Kinghorn

Abstract

During the past few years, a group of cyclopenta[b]benzofurans from the plant genus Aglaia has received broad scientific attention as interesting natural product lead compounds with potential anticancer and insecticidal activities. Since the first cyclopenta[b]benzofuran derivative, rocaglamide, from Aglaia elliptifolia, was found to exhibit antileukemic activity in a murine in vivo model, the genus Aglaia has been subjected to further investigation. Over 40 cyclopenta [b]benzofurans have been tested against different human cancer cell lines, and the cumulative results provide some important clues as to how to improve their activity through modification of their chemical structures. The semisynthesis and total synthesis of the cyclopenta [b]benzofurans have been conducted. Although the ultimate molecular target(s) responsible for their antiproliferative activity has not yet been identified, studies on their cellular mechanism of action have demonstrated that some of these compounds inhibit TNF-α or PMA-induced NF-κB activity in T-lymphocytes and induce apoptosis in different human cancer cell lines. Based on the published data thus far, cyclopenta[b]benzofurans offer excellent potential as therapeutic agent candidates in cancer chemotherapy, even if much work still remains to be done for their further development.

Keywords: Aglaia, Meliaceae, flavaglines, cyclopenta[b]benzofurans, cyclopenta[bc]benzopyrans, benzo[b]oxepines, antiproliferative agents, murine in vivo test systems