Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis

作者：Manning Thomas^*; Plummer Sydney; Baker Tess; Wylie Greg; Clingenpeel Amy C; Phillips Dennis

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(20): 4621-4627.

DOI：10.1016/j.bmcl.2015.08.046

• Antibiotic
• Isoniazid
• Resistance
• Copper
• PEG
• Sucrose
• Glucose
• Tuberculosis
• 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 H-1 and C-13 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.

• 出版日期2015-10-15