Design, Synthesis, and Antibacterial Activities of Novel Heterocyclic Arylsulphonamide Derivatives
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Design, synthesis, and antibacterial activities of a series of arylsulphonamide derivatives as probable peptide deformylase (PDF) inhibitors have been discussed. Compounds have been designed following Lipinski’s rule and after docking into the active site of PDF protein (PDB code: 1G2A) synthesized later on. Furthermore, to assess their antibacterial activity, screening of the compound was done in vitro conditions against Gram-positive and Gram-negative bacterial strains. In silico, studies revealed these compounds as potential antibacterial agents and this fact was also supported by their prominent scoring functions. Antibacterial results indicated that these molecules possessed a significant activity against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli with MIC values ranging from 0.06 to 0.29 μM. TOPKAT results showed that high LD50 values and the compounds were assumed non-carcinogenic when various animal models were studied computationally.
KeywordsArylsulphonamides Peptide deformylase inhibitors Antibacterial activity SAR QSTR
Financial assistance in the form of WOS-A fellowship (SR/WOS-A/CS-1053/2014) to Anuradha Singh by the DST, New Delhi is sincerely acknowledged.
Compliance with ethical standards
Conflict of interest
The author(s) declare no competing interests.
- 7.Verma SK, Jat RK, Nagar N, Saharan R, Sharma V, Pandey S, Bansal KA (2011) Novel antibacterial target: peptide deformylase. Pharmacophore 2:114–123Google Scholar
- 10.Sheth A, Alvarez SE, Gardner J, Ran L, Heaney ML, Scheinberg DA (2014) Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc-overexpressing hematopoietic cancers. Cell Death Dis 5:1–9Google Scholar
- 12.Chen C, Wang T, Wu F, Huang W, He G, Ouyang L, Xiang M, Peng C, Jiang Q (2014) Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity. Drug Des Dev Ther 8:1195–1210Google Scholar
- 16.East SP (2014) Actinonin and analogs: inhibitors of bacterial peptide deformylase. In: Marinelli F, Genilloud O (eds) Antimicrobials: new and old molecules in the fight against multi-resistant bacteria. Springer, Berlin, Heidelberg, pp 287–305. ISBN:978-3-642-39967-1 (Print), 978-3-642-39968-8$4 (Online)Google Scholar
- 17.Hansch C, Sammes PG, Taylor JB (1990) Comprehensive medicinal chemistry, vol 2, Chap. 71. Pergamon Press, OxfordGoogle Scholar
- 19.Stokes SS, Albert R, Buurman ET, Andrews B, Shapiro AB, Green OM, McKenzie AR, Otterbein LR (2012) Inhibitors of the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridylyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 2: optimization of physical properties leading to antibacterial aryl sulphonamides. Bioorg Med Chem Lett 22:7019–7023CrossRefGoogle Scholar
- 23.Kennedy JF, Thorley M (1999) Bioseparation. In: Kleeman A, Engel J, Kutscher B, Reichert D (eds) Pharmaceutical Substances, 3rd edn, vol 8. Thieme, Stuttgart, pp 336Google Scholar
- 27.Wilson CO, Gisvold O, Block JH (2004) Wilson and Gisvold’s textbook of organic medicinal and pharmaceutical chemistry, 11th edn. In: Block J, Beale JM (eds) Lippincott Williams and Wilkins, Philadelphia, p 11Google Scholar
- 28.Kim DK, Lee JY, Lee N, Ryu DH, Kim JS, Lee S, Choi JY, Ryu JH, Kim NH, Im GJ, Choi WS, Kim TK (2001) Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues containing a carboxylic acid group in the 5′-sulphonamide moiety of a phenyl ring. Bioorg Med Chem 9:3013CrossRefGoogle Scholar
- 31.Ogden RC, Flexner CW (2001) Protease inhibitors in AIDS therapy. In: Dekker M (ed) Informa Health Care. New York, Basel, pp 27–48Google Scholar
- 33.RSCB protein Data Bank. http://www.rcsb.org/pdb. Accessed 27 July 2013
- 38.National Committee for Clinical Laboratory Standards (1982) Standard methods for dilution antimicrobial susceptibility test for bacteria which grow aerobically, Villanova, Pa. NCCLS, p 242Google Scholar
- 40.Venkataramana CHS, Ramya SKM, Singh SS, Madhavan V (2011) In-silico ADME and toxcity studies of some novel indole derivatives. JAPS 10:159–162Google Scholar
- 42.Caddick S (2001) Thionation of amides using Lawessons reagent; Thioamides. Synthetic 66. doi: 10.1039/SP66