title: Synthesis, characterization, molecular docking and anti-tubercular activity of Plumbagin-Isoniazid Analog and its β-cyclodextrin conjugate.
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), (1)H 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 4 μg/ml) than PLIHZ and PL under 7H9 medium conditions. The standard anti-tubercular compound INH exhibited MIC values of 0.125 and 32 μg/ml under high and low iron conditions, whereas the conjugate PLIHZ exhibited MIC values of 0.5 and 2.0 μg/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.
authors.affiliation: ISTRA, Department of Chemistry, MCE Society's Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India.
authors.forename: Prasad
authors.initials: P
authors.lastname: Dandawate
authors.affiliation: Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Kiranmayi
authors.initials: K
authors.lastname: Vemuri
authors.affiliation: Department of Bioinformatics and Computer Science, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411044, India.
authors.forename: K
authors.initials: K
authors.lastname: Venkateswara Swamy
authors.affiliation: ISTRA, Department of Chemistry, MCE Society's Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India.
authors.forename: Ejazuddin M
authors.initials: EM
authors.lastname: Khan
authors.affiliation: Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India. Electronic address: srimanju@yahoo.com.
authors.forename: Manjula
authors.initials: M
authors.lastname: Sritharan
authors.affiliation: ISTRA, Department of Chemistry, MCE Society's Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India. Electronic address: sbpadhye@hotmail.com.
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D004355:Drug Stability; D007538:Isoniazid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009285:Naphthoquinones / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D009285:Naphthoquinones; D047392:beta-Cyclodextrins; C031215:betadex; D007538:Isoniazid; C014758:plumbagin
keywords: Antitubercular activity; Inclusion complex; Molecular docking; Plumbagin; Plumbagin–Isoniazid Analog; β-Cyclodextrin