Anti-inflammatory Leads From Myxococcus Virescens

Our main goal is to find novel and known bio-medically active compounds from Myxococcus virescens.  This myxobacterium is known to produce the Bengamides, which are a class of compounds also produced by marine sponges.  In 1986, the Crews Lab isolated Bengamides A and B from the sponge Jaspis coriacea.  Of all the Bengamides isolated (~25), Bengamide B was the most active and Novartis conducted a SAR study using this compound.  Laf 389, a structural analog of Bengamide B, entered Anti-Cancer Phase I Clinical Trials in 2000, but was ultimately dropped 2 years later.  Further drug development has been hindered by the complex synthesis of the Bengamides and its analogs.  However, now it is known that Bengamides E and F can be found in M. virescens, a renewable source.  Ten liters of M. virescens were grown and the crude extract was subjected to HPLC to generate a library of semi-pure compounds.  These were tested in a NF-kB luciferase reporter assay, which tests for anti-inflammatory activity.  NF-kB is also implicated in cancer.  Bengamide E showed potent anti-inflammatory effects in the NF-kB luciferase assay that was not accompanied by cytotoxicity.  Our primary efforts are to purify the known Bengamides E and F, as well as elucidate the structure of a new NF-kB active compound using NMR, MS, and other spectroscopic methods.