Four Compounds Suppressing Growth of Mycobacterium tuberculosis

Aims: To demonstrate the efficacy of several small molecular weight compounds having hydrazide groups, for inhibiting the growth of Mycobacterium tuberculosis. To show these same compounds have favorable drug-likeness properties. Study Design: To synthesize tuberculostats and test their antibacterial activity in-vitro. Place and Duration of Study: University of Nebraska, Durham Science Center, 6001 Dodge Street, Omaha NE 68182, and Texas A&M Health Science Center, Department of Microbial Pathogenesis and Immunology, 8447 State Hwy 47, Medical Research and Education Building, Room #3012, Bryan, TX 7780. From January 2015 to June 2015. Methodology: Hydrazide groups were formed by covalently bonding hydrazine onto small molecules having a single aromatic ring by utilizing microwave excitation and evaluating for antibacterial activity. These compounds were placed into tissue culture media at various Original Research Article Bartzatt et al.; JAMPS, 6(4): 1-10, 2016; Article no.JAMPS.24351 2 concentrations and then tuberculosis bacteria were added to determine the level of growth inhibition. Growth inhibition of the bacteria was measured as a function of compound concentration for assessment and comparison. Results: Compounds A, B, C, and D carry hydrazide groups with various substituents that are bonded to a single aromatic ring. All four compounds show zero violations of Rule of 5, indicating favorable absorption and membrane permeation. All four compounds showed greater than 85% growth inhibition of bacteria at concentrations below 50 micrograms per milliliter, while assayed by colony forming units and luminescence. Values of Log BB suggests compounds A and C will have greater penetration into the central nervous system than isoniazid. Conclusion: These four hydrazide compounds induced substantial inhibition of bacterial growth. Microwave excitation for the synthesis of hydrazide compounds is effective. These compounds have favorable drug-likeness properties and are highly effective inhibiting growth of Mycobacterium tuberculosis.