Synthesis, Characterization and Screening of Some Schiff Bases as Potential Antimicrobial Agents.

Schiff bases derived from 4-amino antipyrene were prepared, and IR and NMR spectral analysis characterized their structure. The Schiff bases produced were (1) 4-((4-chlorobenzylidine)amino)- 1,5-dimethyl-1H-pyrazole-3(2H)-one. [SBS-1], (2) 4-((4-hydroxybenzylidine)amino)-1,5-dimethyl- 1H-pyrazole-3(2H)-one. [SBS-2], (3)1,5-dimethyl-2phenyl-4-((3- phenylallylidine)amino) -1Hpyrazole- 3(2H)-one. [SBS-3], (4)4-((4-hydroxy-3-methoxybenzylidine)amino)-1,5- dimethyl-1Hpyrazole- 3(2H)-one. [SBS-4], (5) 4-(benzylidineamino)-1,5 -dimethyl-1H-pyrazole-3(2H)-one. [SBS- 5], (6) 4-((furan-2-ylmethelene)amino)-1,5-dimethyl-1H-pyrazole-3(2H)-one. [SBS-6] and (7) 4-((4- methoxybenzylidine)amino)-1,5- dimethyl-1H-pyrazole-3(2H)-one. [SBS-7]. The antibacterial activity was studied against S. subfava NCIM 2178, B. megaterium ATCC 9885, P. pseudoalcaligenes ATCC 17440, P. vulgaris NCTC 8313, C. freundii ATCC 10787 and E. aerogenes ATCC 13048. The antibacterial activity was done using Agar Ditch method. The antibacterial activity was evaluated in two polar solvents DMSO and DMF. A differential effect of the compounds extracted in a particular solvent (DMSO/DMF) inhibited different bacteria to a different level. It supports the earlier conclusion that antibacterial activity is dependent on molecular structure of the compound, solvent used and the bacterial strain under consideration. However, from the present results, it appears that cinnamaldehyde as side chain with 4-amino antipyrene as central ligand and DMF as a solvent to be best in inhibiting the studied bacterial strains.

Computational modeling and drug designing of Lipoprotein Lipase (LPL) involved in ischemic stroke.

Homology modeling and flexible docking of Lipoprotein Lipase has been studied in silico approach. Blast result was found to have similarity with Lipoprotein Lipase of 83% identity with 1LPA. Active site of LPL protein was identified by CASTP. Large potential drugs were designed for identifying molecules that can likely bind to protein target of interest. The different drug derivatives designed were used for docking with the generated structure, among the 10 derivatives designed, 3rd derivative showed highest docking result. The drug derivatives were docked to the protein by hydrogen bonding interactions and these interactions play an important role in the binding studies. Our investigations may be helpful for further studies.

Modelling and drug designing of glutamate receptor involved in alzheimer’s disease.

Glutamate receptors dysfunction plays an important role in the pathogenesis and disturbance which is probably a secondary phenomenon to other neurochemical, genetic or metabolic changes, and essential to the development of Alzheimer Disease. Glutamate receptors are synaptic receptors, which are located on the membranes of neuronal cells. Glutamate is used to assemble proteins and also it is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the nervous system. In this work we have modeled a three dimensional structure for Glutamate [NMDA] receptor subunit using MODELLER7V7 software with 2RC7 (Crystal Structure of the NR3A Ligand Binding Core Complex with Glycine) as template. With the aid of Molecular dynamics and Molecular simulations studies it was identified that the generated structure was reliable. This structure was used to identify better inhibitor using docking studies. The drug derivatives were docked to the Glutamate receptor structure into the active site containing residues such as ASP21, LEU30, TYR31, HIS59, and MET60. Among the 21 derivatives 14 were docked and 3rd drug derivative showed better docking energy than the others. Our experimental studies can be further used to develop a better drug for Alzheimer disease.