This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The ultimate goal of the proposed biomedical research project is to facilitate creation of a vigorous, sustainable drug discovery research program at Minot State University that will include direct active participation of undergraduate students at all levels. Specifically, the proposed biomedical research project will target discovery and development of novel formamide antifungal agents discovered by Dr. Mikhail Bobylev. The discovery of novel formamide antifungal agents was based on the hypothesis that the azole moiety in the molecules of classical azole fungicides may be mimicked and replaced by a formamide moiety. The preliminary results confirmed that the formamide analogs of azole fungicides possess broad spectrum anti-fungal activity and have a novel mode of anti-fungal action, distinctly different of the DMI mechanism of azole fungicides. The main research goals of the proposed biomedical research project include: 1) Discovery and development of new patentable anti-fungal drugs based on the novel formamide template. 2) Investigation of structure-activity relationships and the biochemical mode of action of novel formamide fungicides. The proposed research is directly related to human health issues. The incidence of opportunistic fungal infections has been increasing worldwide despite active research programs devoted to the discovery and development of novel antifungal agents. Opportunistic fungal infections represent significant threat to the patients with compromised immune systems brought on by chemotherapy treatment of cancer, organ transplants, surgery,. A second growing concern is the incidence of drug resistance of fungal pathogens to the currently known classes of antifungal agents used in the clinic. These two factors accentuate the urgency to develop safer and more effective therapeutic agents, and to discover new chemical entities to fight current and drug resistant fungal infections.
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