HARZIPHILONE AND FLEEPHILONE, 2 NEW HIV REV RRE BINDING INHIBITORS PRODUCED BY TRICHODERMA-HARZIANUM/

During the screening of the natural products for their ability to inhi bit the binding of REV (regulation of virion expression) protein to [P -33] labeled RRE (REV responsive element RNA, two novel fungal metabol ites, harziphilone and fleephilone, were isolated from the butanol-met hanol (1 : 1) extract of the fermentation broth of Trichoderma harzian um by bioassay guided fractionation. The structures of these two new c ompounds were established by spectroscopic methods. Harziphilone and f leephilone showed inhibitory activity against the binding of REV-prote in to RBE RNA with IC50 values of 2.0 mu M and 7.6 mu M, respectively. However both compounds did not protect CEM-SS cells from acute HIV in fection at concentration levels up to 209 mu g ml using an NTT dye red uction assay. In addition, harziphilone demonstrated cytotoxicity at 3 8 mu M against the murine tumor cell line M-109.