Anti MDR-TB MICs and Cytotoxicity of New Compounds

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This Core is a service for the PO1 entitled "MDR-TB drugs: Targeting Cell Wall synthesis enzymes". The core is designed to screen the compounds generated by the =Compound Development Module", which include Project 1 and Project 2 by Dr. Lee and Dr. Naismith, respectively, and also from the "Priming the Refinement Cycle Module", specifically interacting with Dr. McNeil, Project 3. We will obtain the MIC value against MDR-TB for two to three thousand compounds per annum using two adeptly defined MIC methods, primarily the microplate Alamar blue method and secondly the radiometric BACTEC 460TB method to confirm the MIC. Compounds exhibiting good MIC values will be tested for bactericidal activity using the time-kill method. The compounds that present efficient MIC values will undergo further for cytotoxicity studies in mammalian cell lines to obtain the IC50 values, the concentration causing 50% loss of mammalian cell viability. Cytotoxicity assays will be performed in Vero cell lines and, as appropriate, in tumor-derived (HepG2) cell lines. The Compounds with selective index (MIC/IC50) higher than 10 will be considered "defined hits" and will be sent forward to Core B for studies in the animal model. The information gleaned in this Core will be supplied back to Drs. Naismith and Lee of the "Compound Development Module" to enable the synthesis of better compounds.