DESIGN AND SYNTHESIS OF NOVEL IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AND THEIR ANTI-BACTERIAL ACTIVITY

  • Pushpalatha Budumuru Department of Chemistry, Institute of Science, Gandhi Institute of Technology and Management Deemed To Be University, Visakhapatnam, Andhra Pradesh, India.
  • Srinivasarao Golagani Department of Chemistry, Institute of Science, Gandhi Institute of Technology and Management Deemed To Be University, Visakhapatnam, Andhra Pradesh, India.
  • Venkata Siva Satyanaryana Kantamreddi Department of Chemistry, Institute of Science, Gandhi Institute of Technology and Management Deemed To Be University, Visakhapatnam, Andhra Pradesh, India.

Abstract

Objective: The present study aims to synthesize a novel derivatives of Imidazo[1,2-a]pyridines and the compounds were evaluated for their antibacterial activity.

Methods: A series of newly synthesized compounds were characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, Fourier transform infrared, mass spectral analysis, and screened for their antibacterial activity by disc diffusion method. Molecular docking studies were performed with a bacterial beta subunit of DNA gyrase using Auto Dock 4.2.6, and the docked conformations were analyzed using visual molecular dynamics.

Results: The structural activity relationship of the synthesized imidazo[1,2-a]pyridine derivatives was studied against Gram-positive and Gram-negative bacteria. Among the synthesized compounds N-benzyl-4-((2-(6-methyl-2-(p-tolyl)imidazo[1,2-a]pyridin-3-yl) acetamido)methyl) benzamide (9a) are possessing high activity against Bacillus subtilis. The zone of inhibition produced by the compound 9a is wider than that of remaining compounds used in this study.

Conclusion: The synthesized compounds exhibited good antibacterial activity in comparison with standard drug streptomycin. This suggests that the compound 9a and its analogs are exerting their activity by probably inhibiting bacterial beta subunit of DNA gyrase.

Keywords: Imidazo[1, 2-a]pyridine, Antibacterial activity, Disc diffusion method, Docking

Author Biographies

Pushpalatha Budumuru, Department of Chemistry, Institute of Science, Gandhi Institute of Technology and Management Deemed To Be University, Visakhapatnam, Andhra Pradesh, India.

Department of chemistry

Research scholar

Srinivasarao Golagani, Department of Chemistry, Institute of Science, Gandhi Institute of Technology and Management Deemed To Be University, Visakhapatnam, Andhra Pradesh, India.
 

References

1. Karaman I, Sahin F, Güllüce M. Antimicrobial activity of aqueous and methanol extracts of Juniperus oxycedrus L. J Ethnopharmacol 2003;85:231-5.
2. Mukherjee PK, Saritha GS, Suresh B. Antimicrobial potential of two different Hypericum species available in India. Phytother Res 2002;16:692-5.
3. Puerstinger G, Paeshuyse J, Declercq E, Neyts J. Antiviral 2, 5-disubstituted imidazo[4,5-c]pyridines from anti-pestivirus to anti-hepatitis C virus activity. Bioorg Med Chem Lett 2007;17:390-3.
4. Katsura Y, Nishino S, Inowe Y, Tomoi M, Takasugi H. Studies on antiulcer drugs II synthesis and antiulcer activities of imidazo[1,2-a]pyridinyl- 2-alkylaminobenzoxazoles and 5,6,7,8-tetrahydroimidazo[1,2-a] pyridinyl derivatives. Chem Pharm Bull 1992;40:371-80.
5. Rewankar GR, Matthews JR, Robins RK. Synthesis and antimicrobial activity of certain imidazo[1,2-a]pyrimidines. J Med Chem 1975;18:1253-5.
6. Rival Y, Grassy G, Michel G. Synthesis and antibacterial activity of some imidazo[1,2-a]pyrimidine derivatives. Chem Pharm Bull 1992;40:1170-6.
7. Fisher MH, Lusi A. Imidazo [1,2-a] pyridine anthelmintic and antifungal agents. J Med Chem 1972;15:982-5.
8. Rival Y, Grassy G, Taudou A, Ecalle R. Antifungal activity in vitro of some imidazo[l,2-alpyrimidine derivatives. Eur J Med Chem 1991;26:13-8.
9. Biftu T, Feng D, Fisher M, Liang G, Qian X, Scribner A, et al. Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents. Bioorg Med Chem Lett 2006;16:2479-83.
10. Ismail MA, Arafa RK, Wenzler T, Brun R, Tanious FA, Wilson WD, et al. Synthesis and antiprotozoal activity of novel bis-benzamidinoimidazo [1,2-a] pyridines and 5,6,7,8-tetrahydro-imidazo [1,2-a] pyridines. Bioorg Med Chem 2008;16:683-91.
11. Gudmundsson KS, Johns BA. Imidazo [1,2-a] pyridines with potent activity against herpesviruses. Bioorg Med Chem Lett 2007;17:2735-9.
12. Maruyama Y, Anami K, Terasawa M, Goto K, Imayoshi T, Kadabe Y, et al. Anti-inflammatory activity of an imidazopyridine derivative (miroprofen), Arzneimittel Forsch 1981;31:1111-5.
13. Abignente E, Carariis P, Fattorusso E, Mayol L. Research on heterocyclic compounds XXIII phenyl derivatives of fused imidazole systems. J Heteroc Chem 1989;26:1875-80.
14. Moraski GC, Markley LD, Hipskind PA, Boshoff H, Cho S, Franzblau SG, et al. Advent of Imidazo[1,2-a]pyridine-3-carboxamides with potent multi and extended drug resistant antituberculosis activity. ACS Med Chem Lett 2011;2:466-70.
15. Bhardwaja V, Malleshappa NN, Jalhan S, Patel HM. Synthesis, and antimicrobial evaluation of new pyridine imidazo [2,1b]-1,3,4- thiadiazole derivatives. J Saudi Chem Soc 2016:20;S406-10.
16. Aanandhi MV, Bhattacherjee D, Kamalraj R. Synthesis, docking and biological activity of various substituted zolpidem based GABAA inhibitors endowed potent hypnotic and sedative activity. Med Chem 2014;2:1-8.
17. van Duin D, Paterson D. Multidrug resistant bacteria in the community: Trends and lessons learned. Infect Dis Clin North Am 2016;30:377-90.
18. Sanjay MW, Ghorpade MV, Shivali VG, Annapurna GS, Rashmi MK. A study of vancomycin resistanct Enterococci isolated from urinary tract infections. Int J Pharm Pharm Sci 2015;7:337-9.
19. Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st Century. Perspect Med Chem 2014;6:25-64.
20. Balakrishnan J, Appalasamy JR. Skin infection and the global challenges: A Review. Int J Pharm Pharm Sci 2016;8:1-3.
Statistics
381 Views | 420 Downloads
Citatons
How to Cite
Budumuru, P., S. Golagani, and V. S. S. Kantamreddi. “DESIGN AND SYNTHESIS OF NOVEL IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AND THEIR ANTI-BACTERIAL ACTIVITY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 8, Aug. 2018, pp. 252-8, doi:10.22159/ajpcr.2018.v11i8.26241.
Section
Original Article(s)