Skip to main content

Advertisement

SpringerLink
Log in

Antimicrobial evaluation, QSAR and docking studies of amide-linked 1,4-disubstituted 1,2,3-bistriazoles

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

A series of amide-linked 1,4-disubstituted 1,2,3-bistriazoles was tested for antimicrobial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative bacteria Escherichia coli and two fungal strains Aspergillus niger and Candida albicans. The antimicrobial evaluation data indicated that most of the compounds exhibited potential activity. To describe activity on the structural basis, QSAR studies were performed and statistically significant models were developed. Further, binding interactions of two active compounds 17 and 10 to active sites of E. coli topoisomerase II DNA gyrase B and C. albicans lanosterol 14α-demethylase (1.14.13.70) (CYPLI) (cytochrome P450 51) enzymes, respectively, were also examined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  • Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22:195–201

    Article  CAS  PubMed  Google Scholar 

  • AutoDock Tools (version 1.5.6 rc2), Stefano Forte. Molecular Graphics Laboratory, Department of Molecular Biology, The Scripps Research Institute, (1999–2010) http://mgltools.scripps.edu

  • Bakunov SA, Bakunova SM, Wenzler T, Ghebru M, Werbovetz KA, Brun R, Tidwell RR (2010) Synthesis and antiprotozoal activity of cationic 1,4-diphenyl-1H-1,2,3-triazoles. J Med Chem 53(1):254–272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Benkert P, Biasini M, Schwede T (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27(3):343–350

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Biasini M, Bienert S, Waterhouse A, Arnold K, Studer G, Schmidt T, Kiefer F, Cassarino TG, Bertoni M, Bordoli L, Schwede T (2014) SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res 42:252–258

    Article  Google Scholar 

  • Cao X, Sun Z, Cao Y, Wang R, Cai T, Chu W, Hu W, Yang Y (2014) Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J Med Chem 57(9):3687–3706

    Article  CAS  PubMed  Google Scholar 

  • Cappucino JG, Sherman N (1999) Microbiology—a laboratory manual, 4th edn. Addison Wesley Longman Inc., Harlow, p 263

    Google Scholar 

  • Discovery Studio v4.0 client, Accelrys Software Inc. (2005–2014)

  • Dudek AZ, Arodzb T, Gálvez J (2006) Computational methods in developing quantitative structure-activity relationships (QSAR): a review. Comb Chem High Throughput Screen 9(3):213–228

    Article  CAS  PubMed  Google Scholar 

  • Dunbrack RL (2002) Rotamer libraries in 21st century. Curr Opin Struct Biol 12(4):431–440

    Article  CAS  PubMed  Google Scholar 

  • Furusjo E, Svenson A, Rahmberg M, Andersson M (2006) Chemosphere 63(1):99–108

    Article  PubMed  Google Scholar 

  • Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR et al (2000) Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. J Med Chem 43(5):953–970

    Article  CAS  PubMed  Google Scholar 

  • Ghose AK, Crippen GM (1986) Atomic physicochemical parameters for three-dimensional structure-directed quantitative structure-activity relationships. I. Partition coefficients as a measure of hydrophobicity. J Chem Inf Comput Sci 7:565–577

    Article  CAS  Google Scholar 

  • Ghose AK, Crippen GM (1987) Atomic physicochemical parameters for three-dimensional-structure-directed quantitative structure-activity relationships. Modeling dispersive and hydrophobic interactions. J Chem Inf Comput Sci 27(1):21–35

    Article  CAS  PubMed  Google Scholar 

  • Golbraikh A, Tropsha A (2002) Beware of q2! J Mol Graph Model 20(4):269–276

    Article  CAS  PubMed  Google Scholar 

  • Gramatica P (2007) Principles of QSAR models validation: internal and external. QSAR Comb Sci 26(5):694–701

    Article  CAS  Google Scholar 

  • Ji H, Zhang W, Zhou Y, Zhang M, Zhu J, Song Y, Lu¨ J, Zhu J (2000) A three-dimensional model of Lanosterol 14α-Demethylase of Candida albicans and its interaction with azole antifungals. J Med Chem 43(13):2493–2505

    Article  CAS  PubMed  Google Scholar 

  • Kaushik CP, Lal K, Kumar A, Kumar S (2014) Synthesis and biological evaluation of amino acid-linked 1,2,3-bistriazole conjugates as potential antimicrobial agents. Med Chem Res 23(6):2995–3004

    Article  CAS  Google Scholar 

  • Kier LB, Hall LH (1976) Molecular connectivity in chemistry and drug research. Academic Press, New York

    Google Scholar 

  • Kumar A, Kumar S, Jain S, Kumar P, Goyal R (2013) Study of binding of pyridoacridine alkaloids on Topoisomerase II using in silico tools. Med Chem Res 22(11):5431–5441

    Article  CAS  Google Scholar 

  • Lal K, Kaushik CP, Kumar K, Kumar A, Qazi AK, Hamid A, Jaglan S (2014) One-pot synthesis and cytotoxic evaluation of amide-linked 1,4-disubstituted 1,2,3-bistriazoles. Med Chem Res 23(8):4761–4770

    Article  CAS  Google Scholar 

  • Lauria A, Delisi R, Mingoia F, Terenzi A, Martorana A, Barone G, Almerico AM (2014) 1,2,3-Triazole in heterocyclic compounds, endowed with biological activity, through 1,3-dipolar cycloadditions. Eur J Org Chem 16:3289–3306

    Article  Google Scholar 

  • Liu S, Cao C, Li Z (1998) Approach to estimation and prediction for normal boiling point (NBP) of alkanes based on a novel molecular distance edge (MDE) Vector, lambda. J Chem Inf Comput Sci 38:387–394

    Article  CAS  Google Scholar 

  • Na YM (2011) Synthesis and activity of novel 1-halogenobenzylindole linked triazole derivatives as antifungal agents. Bull Korean Chem Soc 32(1):307–310

    Article  CAS  Google Scholar 

  • Mavin Sketch 5.10.1 ChemAxon Ltd. (1998–2012) http://www.chemaxon.com

  • Ostrov DA, Prada JAH, Corsino PE, Finton KA, Le N, Rowe TC (2007) Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening. Antimicrob Agents Chemother 51(10):3688–3698

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Patpi SR, Pulipati L, Yogeeswari P, Sriram D, Jain N, Sridhar B, Murthy R, Devi AT et al (2012) Design, synthesis, and structure-activity correlations of novel dibenzo[b, d]furan, dibenzo[b, d]thiophene, and N-methylcarbazole clubbed 1,2,3-triazoles as potent inhibitors of Mycobacterium tuberculosis. J Med Chem 55(8):3911–3922

    Article  CAS  PubMed  Google Scholar 

  • Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF chimera a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612

    Article  CAS  PubMed  Google Scholar 

  • Puzyn T, Leszczynski J, Cronin MTD (2010) Recent advances in QSAR studies: methods and applications. Cronin MTD quantitative structure–activity relationships (QSAR)—applications and methodology, 8th edn. Springer, New York, pp 3–11

    Google Scholar 

  • PyMOL(TM) Molecular Graphics System, Version 0.99rc6, Copyright © 2006 DeLano Scientific LLC

  • Singh P, Raj R, Kumar V, Mahajan MP, Bedi PM, Kaur T, Saxena AK (2012) 1,2,3-Triazole tethered β-lactam-chalcone bifunctional hybrids: synthesis and anticancer evaluation. Eur J Med Chem 47(1):594–600

    Article  CAS  PubMed  Google Scholar 

  • Stanton DT, Jurs PC (1990) Development and use of charged partial surface area structural descriptors in computer assisted quantitative structure property relationship studies. Anal Chem 62(21):2323–2329

    Article  CAS  Google Scholar 

  • Surineni G, Yogeeswari P, Sriram D, Kantevari S (2015) Rational design, synthesis and evaluation of novel-substituted 1,2,3-triazolylmethyl carbazoles as potent inhibitors of Mycobacterium tuberculosis. Med Chem Res 24(3):1298–1309

    Article  CAS  Google Scholar 

  • Todeschini R, Gramatica P (1997) The Whim theory: new 3D molecular descriptors for QSAR in environmental modeling. SAR and QSAR Environ Res 7:89–115

    Article  CAS  Google Scholar 

  • Todeschini R, Gramatica P (1998) New 3D molecular descriptors: the WHIM theory and QAR applications. Persepect Drug Discov 9:355–380

    Article  Google Scholar 

  • Todeschini R, Lasagni M, Marengo E (1994) New molecular descriptors for 2D and 3D structures. J Chemom 8:263–272

    Article  CAS  Google Scholar 

  • Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 31(2):455–461

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang J, Wang W, Kollman PA, Case DA (2006) Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Model 25(2):247–260

    Article  PubMed  Google Scholar 

  • Whiting M, Tripp JC, Lin YC, Lindstorm W, Olson AJ, Elder JH, Sharpless KB, Fokin VV (2006) Rapid discovery and structure activity profiling of novel inhibitors of human immunodeficiency virus type 1 protease enabled by the copper(I)-catalyzed synthesis of 1,2,3-triazoles and their further functionalization. J Med Chem 49(26):7697–7710

    Article  CAS  PubMed  Google Scholar 

  • Yap CW (2011) PaDEL-Descriptor: an open source software to calculate molecular descriptors and fingerprints. J Comput Chem 32(7): 1466–1474

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are highly thankful for financial assistance from University Grants Commission, New Delhi.

Author information

Authors and Affiliations

  1. Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, 125001, Haryana, India

    Kashmiri Lal & C. P. Kaushik

  2. Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science andTechnology, Hisar, 125001, Haryana, India

    Ashwani Kumar

Authors
  1. Kashmiri Lal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. P. Kaushik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashwani Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kashmiri Lal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lal, K., Kaushik, C.P. & Kumar, A. Antimicrobial evaluation, QSAR and docking studies of amide-linked 1,4-disubstituted 1,2,3-bistriazoles. Med Chem Res 24, 3258–3271 (2015). https://doi.org/10.1007/s00044-015-1378-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-015-1378-9

Keywords

Search

Navigation