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Sunday, 19 May 2013

Cationic fullerene quinazolinone conjugates as Tuberculosis HGPRT Inhibitors


Synthesis and biological evaluation of cationic fullerene quinazolinone conjugates and their binding mode with modeled Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase enzyme.


Patel MB, Kumar SP, Valand NN, Jasrai YT, Menon SK.

Department of Chemistry, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India. Department of Bioinformatics, Applied Botany Centre, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India.
The present work reports a series of novel cationic fullerene derivatives bearing a substituted-quinazolinone moiety as a side arm. Fullerene-quinazolinone conjugates synthesized using the 1,3-dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted quinazolinone were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR and ESI-MS and screened for their antibacterial activity against Mycobacterium tuberculosis (H 37 Rv strain). All the compounds exhibited significant activity with the most effective having MIC in the range of 1.562-3.125 μg/mL. Compound 9f exhibited good biological activity compared to standard drugs. We developed a computational strategy based on the modeled M. tuberculosis hypoxanthine-guanine phosphoribosyltransferase (HGPRT) using homology modeling techniques and studied its binding pattern with synthesized fullerene derivatives. We then explored the surface geometry of the protein to place the cage adjacent to the active site while optimizing its quinazolinone side arm to establish H bonding with active site residues.

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Artemisinin Molecular Target

Structural Insights into the Theoretical Model of Plasmodium falciparum NADH Dehydrogenase and its Interaction with Artemisinin and Derivatives: Towards Global Health Therapeutics.


Kumar SP, Jasrai YT, Pandya HA, George LB, Patel SK.

Department of Bioinformatics, Applied Botany Centre, University School of Sciences , Gujarat University, Ahmedabad, India .

Abstract
It is a continuing quest to uncover the principal molecular targets of malarial parasites to understand the antimalarial activity and mechanism of action of artemisinin, a potent antimalarial. A series of parasite proteins are experimentally validated as potential targets, such as translationally controlled tumor protein (TCTP) and sarco/endoplasmic reticulum membrane calcium ATP-ase (SERCA). The present study addressed the development of a theoretical model of Plasmodium falciparum NADH dehydrogenase with inference from artemisinin in vivo inhibitory activity. We report here the predicted binding modes of artemisinin and its derivatives. The modeled protein resembled the structural architecture of flavoproteins and oxidoreductases, consisting of two Rossmann folds and dedicated binding sites for its cofactors. Docked poses of the ligand dataset revealed its interactions at or near the si face, indicating being activated. This may aid in generation of reactive oxygen species, thereby disrupting the membrane potential of parasite mitochondria and leading to the clearance from the blood. These observations open up new strategies for development of novel therapeutics, or improvement of existing pharmacotherapies against malaria, a major burden for global health.



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Novel cationic fullerene derivatized s-triazine scaffolds


Novel cationic fullerene derivatized s-triazine scaffolds as photoinduced DNA cleavage agents: design, synthesis, biological evaluation and computational investigation

a. Department of Chemistry, University School of Sciences, Gujarat University, Navrangpura, India 
b. Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Gujarat University, Navrangpura, India
c. Department of Zoology and Biomedical Technology, University School of Sciences, Gujarat University, Navrangpura, India

Graphical abstract: Novel cationic fullerene derivatized s-triazine scaffolds as photoinduced DNA cleavage agents: design, synthesis, biological evaluation and computational investigation


A series of novel cationic fullerene (C60) derivatives, bearing substituted s-triazine moiety as a side arm, synthesized by using the 1,3 dipolar cycloaddition reaction of C60 with azomethine ylides generated from the corresponding Schiff bases of substituted s-triazine is reported. All the synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR and ESI-MS. The compounds 7a7d7e and 7f cleaved the supercoiled pBR322 DNA into nicked form efficiently upon visible light irradiation in the presence of NADH. The photoinduced superoxide radical and hydroxyl radical generated may act as molecular species causing the DNA scission. Further, the interaction of synthesized molecules with pBR322 plasmid DNA was investigated using computational approaches.

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Thursday, 6 December 2012

Evolutionary and Molecular Aspects of Indian Tomato Leaf Curl Virus Coat Protein

Sivakumar Prasanth Kumar, Saumya K. Patel, Ravi G. Kapopara,
Yogesh T. Jasrai, and Himanshu A. Pandya

Department of Bioinformatics, Applied Botany Center, University School of Sciences, Gujarat University, Ahmedabad 380 009, India
Department of Botany, University School of Sciences, Gujarat University, Ahmedabad 380 009, India

Tomato leaf curl disease (ToLCD) is manifested by yellowing of leaf lamina with upward leaf curl, leaf distortion, shrinking of the leaf surface, and stunted plant growth caused by tomato leaf curl virus (ToLCV). In the present study, we explored the evolutionary and molecular prospects of viral coat protein derived from an isolate of Vadodara district, Gujarat (ToLCGV-[Vad]), India. We found that the amino acids in coat protein required for systemic infection, viral particle formation, and insect transmission to host cells were conserved amongst Indian strains. Phylogenetic studies on Indian ToLCV coat proteins showed evolutionary compatibility with other viral taxa. Modeling of coat protein revealed a topology similar to characteristic Geminate viral particle consisting of antiparallel β-barrel motif with N-terminus α-helix. The molecular interaction of coat protein with the viral DNA required for encapsidation and nuclear shuttling was investigated through sequence- and structure-based approaches. We further emphasized the role of loops in coat protein structure as molecular recognition interface.



Thursday, 16 August 2012

Biocomputational Analysis of Filaggrin Sequence Repeats for Rheumatoid Arthritis


Sivakumar Prasanth Kumar 1, Saumya K. Patel 1, Yogesh T. Jasrai *1, Himanshu A. Pandya 1 and Pappu Srinivasan 2

1. Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Gujarat University, Ahmedabad - 380 009, India
2. Department of Bioinformatics, Science Block, Alagappa University, Karaikudi - 630 004, India.

Electronic Journal of Biology, 2012, Vol. 8(2): 29-33

You may access the complete text here: http://www.ejbio.com/pps/2012/29.pdf


Abstract

Anti-citrullinated antibodies are autoantibodies detected in the blood of rheumatoid arthritis (RA) patients in the early stage. These autoantibodies recognize an epitope of citrullinated peptides found on the surface of filaggrin protein and are crossreactive in immune response. Since the expression of filaggrin protein is associated with autoantibodies secretion, it may act as a potential serological marker for the detection of RA in early stage. In the present study, the contribution of filaggrin sequence repeats towards antigenicity was investigated using bioinformatic approaches. The electrostatic potential of citrullinated filaggrin repeats and its antigenicity was found to be the prominent factors for invoking such an immune response.

Keywords: Anti-citrullinated antibodies, epitope, filaggrin sequence repeats, rheumatoid arthritis, electrostatic potential, antigenicity.


Friday, 27 July 2012

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Friday, 29 June 2012

Exploring the polymerase activity of chikungunya viral non structural protein 4 (nsP4) using molecular modeling, epharmacophore and docking studies

S. Prasanth Kumar, Ravi G. Kapopara, Mehul I. Patni, Himanshu A. Pandya, Yogesh T. Jasrai and Saumya K. Patel. Exploring the Polymerase Activity of Chikungunya Viral non structural Protein 4 (nsP4) using Molecular Modeling, e-Pharmacophore and Docking Studies.International Journal of Pharmacy and Life Sciences 3(6): 1752-1765.


Abstract



Chikungunya viral RNA-dependent RNA polymerase (RdRp) activity is conferred by non structural protein 4
(nsp4), an important protein target towards the development of antiviral compounds. The present study deals about the development of homology model of nsP4 followed by molecular docking with known RdRp inhibitors
experimented in Hepatitis C virus (HCV), HIV-1, Paramyxovirus, etc. The predicted catalytic site and two allosteric binding sites were docked with nucleosidic and non-nucleosidic inhibitors. The best top five scoring ligands were selected based upon the interaction profiles and a common pharmacophore was developed. Further, RNA templateprimer complex was docked within the template tunnel of modeled nsP4 to study the mode of polymerase activity.


Key-Words: Chikungunya, nsP4, RdRp, Docking, Pharmacophore, Polymerase activity



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http://www.ijplsjournal.com/issues%20PDF%20files/june_2012/5.pdf