The natural product peptidimetic actinonin demonstrates antiproliferative, antiangiogenic, and antimetastatic properties against many human cancers, including leukemia and lymphoma, as well as against lung and prostate tumors, both in vitro and in vivo. An improved method for the asymmetric synthesis of (S,S,R)-(-)-actinonin allows for inexpensive and abundant production of this compound and novel analogs.
Actinonin and actinonin analogs were assayed for cytotoxity in human prostate, lymphoma, and acute myeloid leukemia cells. Actinonin and some of its analogs are remarkably cytotoxic in the µM range against all the cancer cell lines tested.
Although actinonin is commercially available and usually extracted from bacteria, the yield of actinonin derived in this way is miniscule. The present synthetic pathway improves the synthesis of actinonin and allows for the synthesis of novel analogs, which may have improved efficacy.
Actinonin analogs with improved solubility and inhibitory capacity currently being investigated
- William G. Bornmann, PhD
David A. Scheinberg, MD, PhD, Program Chair and Laboratory Head, Molecular Pharmacology & Chemistry Program, Sloan Kettering Institute, Memorial Sloan Kettering
U.S. patent issued: 6, 887, 887
Lee MD, et al. (2004) J Clin Invest. 114:1107-1116