Dr. Mark E. Janik
Assistant Professor of Chemistry
215 Houghton Hall
SUNY College at Fredonia
Fredonia, NY 14063
Tel: (716) 673-3508
Fax: (716) 673-3347
Mark.Janik@Fredonia.edu

My research interests are in the area of synthetic organic/medicinal chemistry. I am currently involved with two projects. The compound colchicine (Figure 1) is a known antimitotic agent. It exerts its anticancer effect by binding to the protein tubulin. This binding inhibits the polymerization of tubulin and hence stops the mitotic cycle. The binding mechanism of colchicine to tubulin, however, is at this time not fully understood. In addition, colchicine though highly potent is also highly toxic. As a result, its clinical usefulness is severely limited. Thus, the goal of this project is to investigate the colchicine-tubulin interaction and to develop clinically improved colchicine-like drugs. This will be accomplished by synthesizing compounds that bind to the colchicine site on tubulin. The biological activity of these compounds will then be tested and these activities will be compared to those of other colchicine-like compounds. This comparison will help further elucidate the binding mechanism of these drugs and it will also provide compounds with potentially improved clinical utility and less toxic side effects as compared to colchicine.
A second project involves the synthesis of compounds that can act as antibacterial agents of the bacteria Pseudomonas aeruginosa. P. aeruginosa is a ubiquitous gram-negative bacterium that is capable of infecting a wide variety of plants, animals and humans. P. aeruginosa rarely causes disease in healthy individuals but rather infects people with impaired host defense systems such as in cystic fibrosis (CF), cancer, AIDS, diabetes, deep burns and wounds. The typical treatment for such infections consists of anti-pseudomonal antibiotics, such as b-lactams, aminoglycosides and quinolones, however, P. aeruginosa typically develops resistance to these drugs. Therefore, an antibiotic agent that is immune to this resistance is currently needed. The ability of P. aeruginosa to cause cell damage is controlled by an intricate signaling system known as quorum sensing (QS). In the QS system autoinducer molecules (Figure 2) are produced and then subsequently bind to various R proteins. This binding triggers a series of events that ultimately leads to the production of virulence factors that cause cell death in individuals. As a result, the key to stopping infection by P. aeruginosa lies in synthesizing compounds that can act as antagonists of these autoinducer molecules. These antagonist compounds will prevent the autoinducer compounds from binding to the R proteins that in turn will prevent the production of virulence factors by the bacteria.