title: Homology modeling and QSAR analysis of 1,3,4-thiadiazole and 1,3,4-triazole derivatives as carbonic anhydrase inhibitors.
abstract: Carbonic anhydrase (CA) inhibitors are very interesting target for designing anticancer (hypoxic) and antiglaucoma drugs. In the present study, a 3D homology modeling of human carbonic anhydrase-IX (hCA-IX) isozyme, based upon the crystal structure of murine CA-XIVA (PDB CODE 1RJ5) was performed, as no experimental 3D structures are available. A homology model of hCA-IX was developed and validated. To explore the responsible physicochemical properties of 1,3,4-thiadiazole and 1,3,4-triazole derivatives for carbonic anhydrase inhibition, a quantitative structure activity relationship (QSAR) study was performed having hCA-II and hCA-IX inhibitory activity respectively. In hCA-II and hCA-IX inhibitory activities, four significant models with good correlations (> or = 0.945 & > or = 0.926) were obtained; two models (models 1 and 3) were selected based on statistical criterion. The QSAR study revealed that in case of hCA-II, overall increase in size and volume of molecule, introduction of electropositive surfaces might increase the inhibitory activity, whereas in case of hCA-IX, decreasing the hydrophobicity and introduction of electron releasing substituents might increase the hCA-IX inhibitory activity.
authors.affiliation: Computer Aided Drug Design Lab, Department of Pharmacy, Shri Govindram Seksaria Institute of Technology and Science, 23, Park Road, Indore 452 003, (M. P.), India.
authors.forename: N V Murali Krishna
authors.initials: NV
authors.lastname: Akula
authors.forename: Surendra
authors.initials: S
authors.lastname: Kumar
authors.forename: Vineet
authors.initials: V
authors.lastname: Singh
authors.forename: Meena
authors.initials: M
authors.lastname: Tiwari
mesh_terms: D000595:Amino Acid Sequence; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004583:Electrons; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015233:Models, Statistical; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D021281:Quantitative Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013830:Thiadiazoles; D014230:Triazoles; C058949:1,3,4-thiadiazole