Nano-MoO3-mediated synthesis of bioactive thiazolidin-4-ones acting as anti-bacterial agents and their mode-of-action analysis using in silico target prediction, docking and similarity searching

The efficacy of thiazolidin-4-ones as synthons for diverse biological small molecules has given impetus to anti-bacterial studies. Our work aims to synthesize novel bioactive thiazolidin-4-ones using nano-MoO3 for the first time. The compelling advantage of using nano-MoO3 is that the recovered nano-MoO3 can be reused thrice without considerable loss of its catalytic activity. The synthesized thiazolidin-4-ones were tested for anti-bacterial activity against two strains of pathogenic bacteria, namely, Salmonella typhi and Klebsiella pneumoniae. Our results indicated that 3-(benzo[d]isoxazol-3-yl)-2-(3-methoxyphenyl)thiazolidine-4-one (compound 3b) showed significant inhibitory activity towards Salmonella typhi, in comparison with gentamicin. Furthermore, in silico target prediction presented the target of compound 3b as the FtsK motor domain of DNA translocase of Salmonella typhi. Hence, our hypothesis is that compound 3b may disrupt chromosomal segregation and thereby inhibit the division of Salmonella typhi. In addition, similarity searching showed that 34 compounds with a chemical similarity of 70% or higher to compound 3b, which were retrieved from ChEMBL, bound to targets associated with biological processes related to cell development in 36% of the cases. In summary, our work details novel usage of nano-MoO3 for the synthesis of novel thiazolidin-4-ones possessing anti-bacterial activity, and presents a mode-of-action hypothesis.

[1]  L. Csonka.  A third L-proline permease in Salmonella typhimurium which functions in media of elevated osmotic strength , 1982, Journal of bacteriology.

[2]  Andreas Bender,et al.  Fishing the target of antitubercular compounds: in silico target deconvolution model development and validation. , 2009, Journal of proteome research.

[3]  Evan Bolton,et al.  PubChem's BioAssay Database , 2011, Nucleic Acids Res..

[4]  R. Wilson,et al.  Complete genome sequence of Salmonella enterica serovar Typhimurium LT2 , 2001, Nature.

[5]  Lewis H. Mervin,et al.  A Nano-MgO and Ionic Liquid-Catalyzed ‘Green’ Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51) , 2015, PloS one.

[6]  Basappa,et al.  Synthesis of 1,2-benzisoxazole tethered 1,2,3-triazoles that exhibit anticancer activity in acute myeloid leukemia cell lines by inhibiting histone deacetylases, and inducing p21 and tubulin acetylation. , 2015, Bioorganic & medicinal chemistry.

[7]  Andreas Bender,et al.  In Silico Target Predictions: Defining a Benchmarking Data Set and Comparison of Performance of the Multiclass Naïve Bayes and Parzen-Rosenblatt Window , 2013, J. Chem. Inf. Model..

[8]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[9]  Basappa,et al.  Microwave-assisted synthesis, characterization and cytotoxic studies of novel estrogen receptor α ligands towards human breast cancer cells. , 2015, Bioorganic & medicinal chemistry letters.

[10]  Yong‐Sheng Hu,et al.  Ordered mesoporous metallic MoO2 materials with highly reversible lithium storage capacity. , 2009, Nano letters.

[11]  John A. Tallarico,et al.  Use of ligand based models for protein domains to predict novel molecular targets and applications to triage affinity chromatography data. , 2009, Journal of proteome research.

[12]  Lorenz C. Blum,et al.  970 million druglike small molecules for virtual screening in the chemical universe database GDB-13. , 2009, Journal of the American Chemical Society.

[13]  Samuel I. Miller,et al.  Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system. , 2009, Bioorganic & medicinal chemistry letters.

[14]  Samuel I. Miller,et al.  Substituted 2-imino-5-arylidenethiazolidin-4-one inhibitors of bacterial type III secretion. , 2008, Journal of medicinal chemistry.

[15]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[16]  Colin L. Raston,et al.  Green chemistry and the health implications of nanoparticles , 2006 .

[17]  Thomas L. Madden,et al.  Domain enhanced lookup time accelerated BLAST , 2012, Biology Direct.

[18]  A. C. Vinayaka,et al.  A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis , 2014, PloS one.

[19]  C. Ramana,et al.  Silica supported MoO3: a mild heterogeneous catalyst for the Beckmann rearrangement and its application to some sugar derived ketoximes , 2004 .

[20]  D. Sherratt,et al.  Decatenation of DNA circles by FtsK‐dependent Xer site‐specific recombination , 2003, The EMBO journal.

[21]  R. Stephenson.  A and V , 1962, The British journal of ophthalmology.

[22]  Basappa,et al.  Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis. , 2015, Organic & biomolecular chemistry.

[23]  Nelly Dubarry,et al.  Multiple regions along the Escherichia coli FtsK protein are implicated in cell division , 2010, Molecular microbiology.

[24]  S. Gaikwad,et al.  Nanosized MoO3 as a reusable heterogeneous catalyst for the synthesis of 2,6-bis(benzylidene)cyclohexanones , 2015 .

[25]  Roger A. Sheldon,et al.  Metal-catalyzed Oxidations of Organic Compounds: Mechanistic Principles and Synthetic Methodology Including Biochemical Processes , 1981 .

[26]  M. A. Sridhar,et al.  Synthesis of new bioactive venlafaxine analogs: novel thiazolidin-4-ones as antimicrobials. , 2006, Bioorganic & medicinal chemistry.

[27]  M. Kazemeini,et al.  Synthesis and characterization of MoO3 nanostructures by solution combustion method employing morphology and size control , 2010 .

[28]  Lars Liljas,et al.  Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella typhimurium , 2002, Molecular microbiology.

[29]  G. P. Nagabhushana,et al.  α-MoO3 nanoparticles: solution combustion synthesis, photocatalytic and electrochemical properties , 2014 .

[30]  John P. Overington,et al.  ChEMBL: a large-scale bioactivity database for drug discovery , 2011, Nucleic Acids Res..

[31]  Amos Bairoch,et al.  Swiss-Prot: Juggling between evolution and stability , 2004, Briefings Bioinform..

[32]  P. Forzatti,et al.  Characterization and reactivity of MoO3/SiO2 catalysts in the selective catalytic oxidation of ammonia to N2 , 2000 .

[33]  Basappa,et al.  Novel synthetic coumarins that targets NF-κB in Hepatocellular carcinoma. , 2015, Bioorganic & medicinal chemistry letters.

[34]  D. Sherratt,et al.  Molecular mechanism of sequence-directed DNA loading and translocation by FtsK. , 2008, Molecular cell.

[35]  R. Stein,et al.  Domain Behavior and Supercoil Dynamics in Bacterial Chromosomes , 2005 .

[36]  Christian Lesterlin,et al.  Asymmetry of Chromosome Replichores Renders the DNA Translocase Activity of FtsK Essential for Cell Division and Cell Shape Maintenance in Escherichia coli , 2008, PLoS genetics.

[37]  Anushya Muruganujan,et al.  PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees , 2012, Nucleic Acids Res..

[38]  John P. Overington,et al.  Chemogenomics approaches for receptor deorphanization and extensions of the chemogenomics concept to phenotypic space. , 2011, Current topics in medicinal chemistry.

[39]  Basappa,et al.  Development of a Novel Azaspirane That Targets the Janus Kinase-Signal Transducer and Activator of Transcription (STAT) Pathway in Hepatocellular Carcinoma in Vitro and in Vivo* , 2014, The Journal of Biological Chemistry.

[40]  Basappa,et al.  Preparation and use of combustion-derived Bi2O3 for the synthesis of heterocycles with anti-cancer properties by Suzuki-coupling reactions , 2014 .