Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis.
The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis.
Chemistry, Valdosta State University, Valdosta, GA 31698, United States. Electronic address: tmanning@valdosta.edu.
Thomas
T
Manning
Chemistry, Valdosta State University, Valdosta, GA 31698, United States.
Sydney
S
Plummer
Chemistry, Valdosta State University, Valdosta, GA 31698, United States.
Tess
T
Baker
NMR Facility, Texas A&M, College Station, TX 77843, United States.
Greg
G
Wylie
FT-ICR Facility, National High Field Magnet Lab, Tallahassee, FL 32310, United States.
Amy C
AC
Clingenpeel
PAMS Facility, Chemistry, University of Georgia, Athens, GA 30602, United States.
Dennis
D
Phillips
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D007538:Isoniazid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D007538:Isoniazid
Antibiotic; Copper; Glucose; Isoniazid; Mycobacterium tuberculosis; PEG; Resistance; Sucrose; Tuberculosis