E-Combretastatin and E-Resveratrol Structural Modifications: Antimicrobial and Cancer Cell Growth Inhibitory Beta-E-Nitrostyrenes

Authors: PETTIT, ROBIN - Arizona State University; PETTIT, GEORGE - Arizona State University; HAMEL, ERNEST - National Cancer Institute (NCI, NIH); HOGAN, FIONA - Arizona State University; Moser, Bryan; WOLF, SONJA - Arizona State University; PON, SANDY - Arizona State University; CHAPUIS, JEAN - Arizona State University; SCHMIDT, JEAN - Arizona State University

Submitted to: Bioorganic and Medicinal Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/30/2009
Publication Date: 8/4/2009
Citation: Pettit, R.K., Pettit, G.R., Hamel, E., Hogan, F., Moser, B.R., Wolf, S., Pon, S., Chapuis, J.C., Schmidt, J.M. 2009. E-Combretastatin and E-Resveratrol Structural Modifications: Antimicrobial and Cancer Cell Growth Inhibitory Beta-E-Nitrostyrenes. Biorganic and Medicinal Chemistry. 17:6606-6612.

Interpretive Summary: This research reveals that chemical compounds less complex but similar to those found in nature have beneficial antimicrobial and anticancer properties. The objective of this study was to prepare potential new therapeutic agents using complex naturally occurring chemicals as templates. The new drug candidates were structurally simpler than the naturally occurring chemicals while still displaying similar antimicrobial and anticancer behaviors. This is beneficial because the naturally occurring chemicals are too complicated to be economically produced on a large scale to be of any benefit to society. This research may ultimately improve human health by providing additional potential therapeutic agents that can be economically produced.

Technical Abstract: As part of a broad-based SAR investigation of E-resveratrol (strong sirtuin activator and antineoplastic) and the anticancer vascular-targeting combretastatin-type stilbenes, a series of twenty-three beta-E-nitrostyrenes was synthesized in order to evaluate potential antineoplastic, antitubulin polymerization, and antimicrobial activities. The beta-E-nitrostyrenes evaluated ranged from monosubstituted phenols to trimethoxy and 3-methoxy-4,5-methylenedioxy derivatives. Two of the beta-nitrostyrenes were synthesized as water-soluble sodium phosphate derivatives (4t, 4v). All except four (4r, 4s, 4t, 4u) of the series significantly inhibited a minipanel of human cancer cell lines. All but eight led to an IC50 of <9.3 OM for inhibition of tubulin polymerization, and all except three (4l, 4t, 4v) displayed antimicrobial activity.