Microwave assisted synthesis of 33 membered parallel library of aryl-and heteroaryl chalcones was carried out by reaction of 3-hydroxyacetophenone with different substituted aryl-and heteroaryl aldehydes under Claisen-Schmidt conditions. The synthesized chalcones are significantly active against Bordetella bronchiseptica (ATCC 4617), gram negative respiratory pathogen that infects wide range of animals and human using cefixime as standard antibiotic as control. Tested compounds show moderate inhibitory activities (zone of inhibition 18.5-10.5 mm) compared to standard (zone of inhibition 13.0). All halogen substituted chalcones are most active members of the library while nitrochalcones and nitrogen containing heteroarylchalcones are least potent and 3-bromochalcone (16) was identified as lead structure of the library. Quantitative structure activity relationship was established to find dependency trend in sterms of bactericidal activity with number of molecular descriptors and some suggestive correlations of activity with these descriptors. Quantitative structure activity relationship was established using MOE software package showing good correlation of activity with various physicochemical parameters e.g. Hammett substituent constant σ, E HOMO , log P and molar volume Vm. It was observed that bactericidal potency of chalcones was dependent more on steric than on electronic descriptors. Chalcones with electron acceptors on phenyl ring and those with greater lipophilic character were expected to be stronger inhibitors of B. bronchiseptica with exception of nitrosubstituted chalcones. This study, therefore, facilitate design and synthesis of chalcones with higher potency to serve as potential inhibitors of B. bronchiseptica, thereby, helping to establish breakpoints for antimicrobial agents for which no systematic study is currently available.
dz-Aminobutyrate aminotransferase (GABA-AT) is a pyridoxal phosphate dependent homodimeric enzyme of 50-kD subunits. It is a potential drug target against epilepsy. The three-dimensional structure of GABA-AT is not experimentally known, and we thus resorted to homology modelling to build a model based on x-ray crystal structure of pig liver GABA-AT to 3.0 Å resolution. Knowledge of the threedimensional structure of GABA-AT would greatly advance the development of novel lead compounds targeting this molecule. The protein's conservity was verified by performing multiple alignments using ClustalW and MUSCLE programs. The model was further checked for its correctness by predicting the 2D and 3D structures, which validates the structure.
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