Novel Tuberculostatic Agents Suitable for Treatment of Mycobacterium tuberculosis Infections of the Central Nervous System
Journal Title: Journal of Pharmaceutical Research International - Year 2014, Vol 4, Issue 12
Abstract
Aims: To demonstrate the efficacy of five small molecule compounds for inhibiting the growth of Mycobacterium tuberculosis. To present evidence that these compounds will penetrate into the central nervous system. Study Design: Five small molecule compounds bearing a hydrazide group were synthesized utilizing microwave excitation. These compounds were then placed into tissue culture with Mycobacterium tuberculosis at various concentrations for evaluation of bacterial growth inhibition. Place and Duration of Study: The compounds to be tested were prepared at the University of Nebraska Chemistry Department August 2013. The evaluation of antibacterial activity was determined at the Texas A&M Health Science Center during October to December of 2013. Methodology: Applying microwave excitation for generation of hydrazide groups within the structure of small molecule carboxylic acids, five agents were prepared for evaluation of bacterial growth inhibition. These agents were dissolved into tissue culture media at various concentrations. Having various levels of tuberculostatic agents, then tuberculosis bacteria were added to determine level of growth inhibition. Growth inhibition of the bacteria was achieved and measured by compound concentration for comparison and evaluation. Results: Five compounds having a hydrazide functional group greatly inhibited the growth of Mycobacterium tuberculosis. All five agents had molecular weight less than 215 grams/mole and polar surface area of less than 70 Angstroms2. Values of Log P ranged from -0.226 to 0.998. Values of Log BB (Log [Cbrain/Cblood]) ranged from -0.711 to - 0.525, with a range in central nervous system penetration Cbrain/Cblood of 0.195 to 0.299. All compounds showed zero violations of the Rule of 5. Substantial inhibition of bacterial growth was observed at concentrations as low as 30 micrograms/mL, as measured by optical density and colony forming units. Conclusion: These five hydrazide compounds substantially decreased the proliferation of tuberculosis bacteria at concentrations as low as 30 micrograms/mL. In addition, their physicochemical properties are shown to allow high levels of penetration into the central nervous system.
Authors and Affiliations
Ronald Bartzatt, Preeti Sule, Suat L. G. Cirillo, Jeffrey D. Cirillo
Keywords
Related Articles
- EP ID EP344761
- DOI 10.9734/BJPR/2014/10353
- Views 76
- Downloads 0
Anti-proliferative Effect of Chickpea Extract on Hela, MCF-7, Saos and Fibroblast Cell Lines
Background and Aim: The present study aimed to investigate the proliferation inhibitory effects of seed protein extract from chickpeas (Cicer arietinum L.) on cancer cell lines. Materials and Methods: The chickpea water...
Endothelin-1 (1-31) Causes the Migration of Vascular Smooth Muscle Cells through Endothelin ETA Receptor
Endothelin-1 (ET-1) is predominantly expressed in endothelial cells to modulate physiological actions, such as vasoconstriction and cell proliferation. It acts as an autocrine and paracrine factor, and has been reported...
Fipronil Induced Hepatotoxicity, Genotoxicity, Oxidative Stress and the Possible Ameliorative Effect of Ginseng
Fipronil (FPN) is a wide-spectrum insecticide and has been extensively used in agriculture since 1990s. The current study was deliberated to inspect the retrograde effects of exposure to the FPN on the hepatic tissues of...
Efficacy of Commercially Used Antibacterial Agents against Oral Bacteria Associated with HIV/AIDS Patients in South Western Uganda
Aims: This was to determine efficacy and resistance profiles against commonly used commercial antibacterial agents in Uganda in the management of oral pathogens in HIV/AIDS patients. Study Design: This was an experimenta...
Review of Drug Interactions: A Comprehensive Update
Prescribing multiple medications predisposes to possibilities of occurrence of drug interactions. Various different terminology and ways exist to classify or arrange drug interactions. Drugs interact with other drugs, fo...