Multi-drug resistance among Gram-positive bacterial pathogens represents a serious challenge for health practitioners. The oxazolidinone class of antimicrobials represents a promising advance in the fight against this resistance. The first oxazolidinone approved for clinical use was linozolid (tradename Zyvox; compound 1 in Fig. 1). Recently, the Ippoliti lab completed the synthesis of a novel oxazolidinone compound containing a benzodioxin ring system (compound 2 in fig. 1) using an efficient seven-step synthesis. The antibacterial activity of this compound was tested in the Ditty lab and shown to have a minimum inhibitory concentration (MIC) of 2-3 µg/mL against Staphylococcus aureus, similar to the MIC of 4 µg/mL for Zyvox (Moellering 2003). This work is in preparation for the Journal of Medicinal Chemistry.
The next objective is to synthesize novel oxazolidinones containing a thiadiazole ring (with general structure of compound 3 in fig. 1). Other compounds containing the thiadiazole ring system have been shown to possess antibacterial properties. The first two compounds to be synthesized and tested will be compound 3 with R group p-methoxyphenyl and ethyl respectively (4 and 5 in fig. 1). Synthesis of the p-methoxyphenyl compound is shown in fig. 2. Synthesis of the ethyl compound will follow the same route but use a different starting material.
Biology and chemistry students involved in these interdisciplinary projects will get hands on experience that clearly demonstrates the interrelatedness of these two disciplines. For each projects, a student and faculty mentor from Biology will collaborate directly with a student-faculty tandem from Chemistry. We expect productive exchanges of information to occur between each member of the four person group; it should be especially empowering for students in one discipline provide guidance to faculty and student peers in the other.
Beyond the paired structure of the research projects, we have also planned ancillary activities to promote the integration of our research programs. Several activities will directly complement student research. These include monthly research group meetings during the academic year to discuss relevant journal articles and preliminary data generated by the project. We will also organize seminars each fall in which researchers participating in the USRP will present their findings to UST Biology and Chemistry majors. We envision presentations where each student integrates their particular findings with those of their partner. These meetings will prepare student researchers for active participation at a national scientific meeting. In short, students participating in the program will serve as ambassadors for interdisciplinary activities.