ABSTRACT
Isoniazid (INH) is known to cause the exclusive lethal action to Mycobacterium tuberculosis (M. tb.) cells because of the pathogen's own catalase-peroxidase (katG) enzyme that converts INH to a very reactive radical. Thus, in order to gain insights on the interaction of INH with the individual active site residues (Res) of katG, this study presents a computational approach via molecular docking and density functional theory (DFT) using augmented models to study the individual INH-Res interactions. Seven amino acid residues directly interacts with INH: Arg104, Asp137, His108, Ile228, Trp107, Tyr229, and Val230. The residues with the highest interaction energies are Arg104 (-39.64â¯kcal/mol) and Asp137 (-32.85â¯kcal/mol) mainly due to strong ion-dipole and H-bonding interactions present in the complexes, while the weakest interaction was observed for Ile228 (-13.78â¯kcal/mol). Molecular electrostatic potential surface revealed complementary regions for dipole interactions and charge distribution analysis further shows that INH generally donates electrons to the residues. The results in this study agrees with the previous experimental findings and provides new insights into the catalase dependent activation of INH and the methods presented may be valuable in the study of biological metabolism of molecules.
Subject(s)
Antitubercular Agents , Bacterial Proteins , Isoniazid , Mycobacterium tuberculosis , Peroxidases , Amino Acids/metabolism , Antitubercular Agents/metabolism , Bacterial Proteins/metabolism , Binding Sites , Computational Biology/methods , Drug Design , Isoniazid/metabolism , Models, Molecular , Molecular Docking Simulation/methods , Mycobacterium tuberculosis/enzymology , Peroxidases/metabolismABSTRACT
The dichloromethane extract of Cespitularia erecta afforded a new verticillane diterpenoid (1) and sarcophytol A (2) by silica gel chromatography. The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy.
Subject(s)
Anthozoa/chemistry , Diterpenes/chemistry , Animals , Diterpenes/isolation & purification , Diterpenes/pharmacology , Molecular StructureABSTRACT
The dichloromethane extract of Xenia viridis afforded two new xenicane diterpenoids (3 and 4) by silica gel chromatography. The oxirane ring of 3 was found to be susceptible to a slow ring opening under acidic conditions to afford 5. Their structures were elucidated by extensive 1D and 2D NMR spectroscopy.
