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Abstract
A novel Plumbagin–Isoniazid Analog (PLIHZ) and its β-cyclodextrin inclusion complex (PLIHZCD) is prepared, characterized and evaluated for antitubercular activity under low and high iron conditions. PLIHZCD inclusion complex was characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction Studies (PXRD), 1H NMR Studies and Scanning Electron Microscopic (SEM) analysis. The orientation and interaction of PLIHZ and CD was studied by molecular docking. PLIHZCD exhibited superior activity (MIC of 4μg/ml) than PLIHZ and PL under 7H9 medium conditions. The standard anti-tubercular compound INH exhibited MIC values of 0.125 and 32μg/ml under high and low iron conditions, whereas the conjugate PLIHZ exhibited MIC values of 0.5 and 2.0μg/ml under high and low iron (corresponding to isoniazid resistant condition) indicating the advantage of combining plumbagin with INH overcoming resistance. The cyclodextrin conjugate offers improved aqueous solubility and thermal stability which are advantages in the treatment protocol.
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