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Synthesis, In Silico Study and Antiurease Potential of Imine Derivatives

  • Muhammad SarfrazEmail author
  • Shahbaz Ahmad
  • Muhammad Ilyas Tariq
  • Muhammad Naeem Qaisar
Research Paper
  • 56 Downloads

Abstract

In search of potent urease inhibitors, we have biologically evaluated our synthesized imine derivatives against jack bean urease. In vitro assay results showed that compound 3f with IC50 value of 16.50 ± 0.20 µM can be considered as the most potent urease inhibitor, whereas compounds 3a (IC50 = 23.10 ± 0.11 µM) and 3n (IC50 = 23.34 ± 0.21 µM) were second and third most potent inhibitors, respectively. In silico study revealed that all compounds have good penetration across BBB and HIA; however, AMES toxicity and carcinogenic profiles of more than half of the compounds were not satisfactory. Leading compound 3f was predicted to have very less penetration across BBB, whereas pharmacokinetic profile of compound 3l was better than all other compounds with no toxicity and carcinogenicity. The synthesized compounds can be used as structural foundation for the preparation of new potent urease inhibitors.

Graphical Abstract

Keywords

Urease inhibitors Peptic ulcers Benzylidenes admetSAR Schiff bases 

Notes

Acknowledgments

Authors of this paper are thankful to Higher Education Commission (HEC) of Pakistan for financial support. We are also thankful to Prof. Dr. Muhammad Nawaz Tahir, University of Sargodha, for XRD analysis and Dr. Muhammad Naeem, University of Sargodha, Pakistan, for biological activity study.

Compliance with Ethical Standards

Conflict of interest

Authors of this research paper declare no conflicts of interest.

References

  1. Amtul Z, Siddiqui RA, Choudhary MI (2002) Chemistry and mechanism of urease inhibition. Curr Med Chem 9:1323–1348CrossRefGoogle Scholar
  2. Bekircan O, Kahveci B, Küçük M (2006) Synthesis and anticancer evaluation of some new unsymmetrical 3, 5-diaryl-4H-1, 2, 4-triazole derivatives. Tur J Chem 30:29–40Google Scholar
  3. Chakraborti AK, Bhagat S, Rudrawar S (2004) Magnesium perchlorate as an efficient catalyst for the synthesis of imines and phenylhydrazones. Tetrahed Lett 45(41):7641–7644CrossRefGoogle Scholar
  4. Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y (2012) admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. Chem Inf Model 52:3099–3105CrossRefGoogle Scholar
  5. de Castro Barbosa ML, Lima LM, Tesch R, Sant’Anna CM, Totzke F, Kubbutat MH, Schächtele C, Laufer SA, Barreiro EJ (2014) Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors. Eur J Med Chem 71:1–14CrossRefGoogle Scholar
  6. Ibrahim MN, Sharif SE (2007) Synthesis, characterization and use of Schiff bases as fluorimetric analytical reagents. J Chem 4(4):531–535Google Scholar
  7. Jamil M, Sultana N, Ashraf R, Sarfraz M, Tariq MI, Mustaqeem M (2017) Urease and Cholinesterase inhibition studies of tris-diamines derived transition metal complexes of Naproxen. SYLWAN 161(9):18–38Google Scholar
  8. Jungreis E, Thabet S (1969) Analytical applications of Schiff bases. Dekker M, New YorkGoogle Scholar
  9. Kahveci B, Bekircan O, Karaoğlu ŞA (2005) Synthesis and antimicrobial activity of some 3-alkyl-4-(arylmethyleneamino)-4, 5-dihydro-1H-1, 2, 4-triazol-5-ones. Indian J Chem 44B:2614–2617Google Scholar
  10. Lehlinger AL (1975) Biochemistry, 2nd edn. Worth Publisher, New York, p 8485220Google Scholar
  11. Li X, Mobley HL (2002) Vaccines for Proteus mirabilis in urinary tract infection. Int J Antimicrobial Agents 19:461–465CrossRefGoogle Scholar
  12. Mahmud T, Rehman R, Gulzar A, Khalid A, Anwar J, Shafique U, Salman M (2010) Synthesis, characterization and study of antibacterial activity of enaminone complexes of zinc and iron. Arab J Chem 3:219–224CrossRefGoogle Scholar
  13. Mobley HL, Hausinger RP (1989) Microbial ureases: significance, regulation, and molecular characterization. Microbiological reviews. Microbiol Rev 53:85–108Google Scholar
  14. Mobley H, Island MD, Hausinger RP (1995) Molecular biology of microbial ureases. Microbiol Rev 59:451–480Google Scholar
  15. Mufakkar M, Tahir MN, Tariq MI, Ahmad S, Sarfraz M (2010) (E)-1- (4-Methoxybenzylidene) -2-phenylhydrazine. Acta Cryst E 66:1887CrossRefGoogle Scholar
  16. Patai S (1970) The Chemistry of the carbon-nitrogen double bond. Wiley, LondonGoogle Scholar
  17. Sarfraz S, Tariq MI, Tahir MN (2010) Synthesis of N-{(E)-[4-(Dimethylamino) phenyl] methylidene}-2,3-dimethylaniline. Acta Cryst E 66:2055CrossRefGoogle Scholar
  18. Sarfraz M, Sultana N, Rashid U, Akram MS, Sadiq A, Tariq MI (2017a) Synthesis, biological evaluation and docking studies of 2, 3-dihydroquinazolin-4 (1H)-one derivatives as inhibitors of cholinesterases. Bioorg Chem 70:237–244CrossRefGoogle Scholar
  19. Sarfraz M, Sultana N, Jamil M, Ashraf R, Ahmad T, Tariq MI (2017b) Synthesis and biological evaluation of 2-aminobenzamide derivatives as inhibitor of cholinesterases and urease enzymes. SYLWAN 161(9):40–62Google Scholar
  20. Shad HA, Tahir MN, Tariq MI, Sarfraz M, Ahmad S (2010) (E)-1-(2-Nitro benzylidene)-2-phenylhydrazine. Acta Cryst E 66:1955CrossRefGoogle Scholar
  21. Shah MR, Soomro ZH (2012) Urease inhibition, enzyme inhibition and bioapplications. In: Sharma R (ed) InTech. ISBN: 978-953-51-0585-5Google Scholar
  22. Sultana N, Sarfraz M, Tanoli ST, Akram MS, Sadiq A, Rashid U, Tariq MI (2017) Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2, 3-dihydroquinazolin-4 (1H)-one as inhibitors of cholinesterases. Bioorg Chem 72:256–267CrossRefGoogle Scholar
  23. Tahir MN, Tariq MI, Sarfraz M, Ahmad S, Tariq RH (2010a) 4-Chloro-N-[(E)-(3,4-dimethoxyphenyl)methylidene]aniline. Acta Cryst E 66:2355CrossRefGoogle Scholar
  24. Tahir MN, Tariq MI, Ahmad S, Sarfraz M (2010b) 2-Hydroxy-5- {[(E)-4-methoxybenzylidene]azaniumyl}benzoate. Acta Cryst E66:2553–2554Google Scholar
  25. Tahir MN, Tariq MI, Ahmad S, Sarfraz M, Ather AQ (2010c) (E)-2, 3-Dimethyl-N-(2-nitrobenzylidene) aniline. Acta Cryst E 66:1817CrossRefGoogle Scholar
  26. Tahir MN, Tariq MI, Ahmad S, Sarfraz M, Tariq RH (2010d) 2,3-Dimethyl-N- [(E)-(1H-pyrrol-2-yl) methylidene]aniline. Acta Cryst E 66:2295CrossRefGoogle Scholar
  27. Tahir MN, Tariq MI, Ahmad S, Sarfraz M, Ather AQ (2010e) N-[(E)-4-Chloro benzylidene]-2, 3-dimethylaniline. Acta Cryst E 66:1562CrossRefGoogle Scholar
  28. Tahir MN, Tariq MI, Ahmad S, Sarfraz M, Tariq RH (2010f) 2-[(E)-(2,3-Dimethylphenyl)iminomethyl] phenol. Acta Cryst E 66:2439CrossRefGoogle Scholar
  29. Tahir MN, Tariq MI, Tariq RH, Sarfraz M (2011) (E)-1-(4-Chlorobenzylidene)-2-phenylhydrazine. Acta Cryst E 67:2377CrossRefGoogle Scholar
  30. Tarafder MT, Kasbollah A, Saravanan N, Crouse KA, Ali AM, Tin OK (2002) S-methyldithiocarbazate and its Schiff bases: evaluation of bondings and biological properties. Journal of biochemistry, molecular biology, and biophysics. J Biochem Mol Biol Biophs 6:85–91CrossRefGoogle Scholar
  31. Tariq MI, Sarfraz M, Tahir MN, Ahmad S, Hussain I (2010a) (2Z)-2-[(2,3-Dimethylphenyl)imino]-1,2-diphenylethanone. Acta Cryst E 66:2078CrossRefGoogle Scholar
  32. Tariq MI, Shahbaz M, Tahir MN, Sarfraz M, Hussain I (2010b) 2, 3-Dimethyl-N-[(E)-4-nitrobenzylidene] aniline. Acta Cryst E 66:1561CrossRefGoogle Scholar
  33. Upadhyay LSB (2012) Urease inhibitor: a review. Indian J Biotech 11:381–388Google Scholar
  34. Vicini P, Geronikaki A, Incerti M, Busonera B, Poni G, Cabras CA, La Colla P (2003) Synthesis and biological evaluation of benzo [d] isothiazole, benzothiazole and thiazole Schiff bases. Bioorg Med Chem 11:4785–4789CrossRefGoogle Scholar
  35. Weatherburn MW (1967) Phenol-hypochlorite reaction for determination of ammonia. Analytical chemistry. Anal Chem 39:971–974CrossRefGoogle Scholar
  36. Zheng Y, Ma K, Li H, Li J, He J, Sun X, Li R, Ma J (2009) One pot synthesis of imines from aromatic nitro compounds with a novel Ni/SiO2 magnetic catalyst. Catal Lett 128(3):465–474CrossRefGoogle Scholar
  37. Zullo A, Rinaldi V, Folino S, Diana F, Attili AF (1998) Helicobacter pylori urease inhibition and ammonia levels in cirrhotic patients. Am J Gastroenterol 93:851–852CrossRefGoogle Scholar

Copyright information

© Shiraz University 2018

Authors and Affiliations

  • Muhammad Sarfraz
    • 1
    Email author
  • Shahbaz Ahmad
    • 1
  • Muhammad Ilyas Tariq
    • 1
  • Muhammad Naeem Qaisar
    • 2
  1. 1.Department of ChemistryUniversity of SargodhaSargodhaPakistan
  2. 2.Department of PharmacyUniversity of SargodhaSargodhaPakistan

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