potent antimicrobial agents Synthesis of quinoline ...1 Synthesis of quinoline acetohydrazide-hydrazone derivatives evaluated as DNA gyrase inhibitors and potent antimicrobial agents
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Synthesis of quinoline acetohydrazide-hydrazone derivatives evaluated as DNA gyrase inhibitors and potent antimicrobial agents
P. Sridhara, Manikandan Alagumuthub, Sivakumar Arumugamb, Sabbasani Rajasekhara Reddya,*
aDepartment of Chemistry, Scholl of Advanced Sciences, VIT University, Vellore-632014, IndiabSchool of Bio-Science and Technology, VIT University, Vellore-632014, India.
9a. R = 4-OMe9b. R = 2,4-OMe9c. R = 2,5-OMe9d. R = 2,6-OMe9e. R = 3,4-OMe9f. R = OEt9g. R = OPr9h. R = 3,4,5-OMe9i. R = 4-F9j. R = 4-OCF39k. R = 4-CF39l. R= 3-CF39m.R = 2,4-F9n. R = 3,4-F
Hydrazine hydrateEthanol
Ethanol
Scheme 1: Synthesis of novel Quinoline acetohydrazide derivatives 9a-9n
Experimental Conditions: a)cinnamoyl chloride, aq. NaHCO3, isopropyl acetate, room temperature, 30 min; b) AlCl3, chlorobenzene, 90 °C, 1 h; c) MeI, KtOBu, DMSO, 70 °C, 2.5 h; d) NBS, benzoyl peroxide, xylene, 70 °C, 1.5 h; e) KCN, DMF, 60 °C, 16 h; f) TMSiCl, MeOH, 70 °C, 2.5 h; g) NH2-NH2, ethanol, reflux, 20 h; h) benzaldehydes, a-n, ethanol, reflux, 4 h.
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Table 1-In vivo efficacy of quinoline acetohydrazide derivatives 9a-9n for demonstrating antibacterial activity against selected pathogens
Zone of inhibition (mM)**Entry CompoundsE.coli P.aeruginosa S.aureus S.pyogenes
*DMSO, **Diameter of well (bore size)- 6 mm; Culture strains of bacteria were maintained on nutrient agar slant at 37±0.5 °C for 24 h; All plates were incubated at 37±0.5 °C for 24 h.
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F N O
NH
O
NH2
Compound 8
Fig. 1:1H NMR spectrum of 2-(7-fluoro-2-methoxyquinolin-8-yl) acetohydrazide
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Fig. 2: Mass spectra of Compound 8
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Fig.3: 1H NMR spectra of 9a
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Fig.4. 13C NMR spectra of 9a
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F N ONH
O
NO
Exact Mass: 367.13
Fig. 5. Mass spectra of 9a
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Fig.6. HRMS spectra of 9a
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Fig. 7. 1H NMR spectra of 9b
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Fig. 8. Mass spectra of 9b
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Fig. 9. 1H NMR spectra of 9c
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Fig. 10. Mass spectra of 9c
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Fig. 11. 1H NMR spectra of 9d
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Fig. 12. Mass spectra of 9d
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Fig. 13. 1H NMR spectra of 9e
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F N ONH
O
N
O
O
Exact Mass: 397.14
9e
Fig. 14. Mass spectra of 9e
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Fig. 15. 1H NMR spectra of 9f
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Fig. 16. Mass spectra of 9f
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Fig. 17. HRMS spectra of 9f
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Fig. 18. 1H NMR spectra of 9g
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Fig. 19. Mass spectra of 9g
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Fig. 20. HRMS spectra of 9g
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Fig. 21. 1H NMR spectra of 9h
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Fig. 22. Mass spectra of 9h
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Fig. 23. HRMS spectra of 9h
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Fig. 24. 1H NMR spectra of 9i
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Fig. 25. Mass spectra of 9i
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Fig. 26. IR spectra of 9i
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Fig. 27. HRMS spectra of 9i
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Fig. 28. 1H NMR spectra of 9j
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Fig. 29. 13C NMR spectra of 9j
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Fig. 30. Mass spectra of 9j
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Fig. 31. IR spectra of 9j
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Fig. 32. HRMS spectra of 9j
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Fig. 33. 1H NMR spectra of 9k
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Fig. 34. 13C NMR spectra of 9k
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Fig. 35. Mass spectra of 9k
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Fig. 36. HRMS spectra of 9k
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Fig. 37. 1H NMR spectra of 9l
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Fig. 38. 13C NMR spectra of 9l
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Fig. 39. Mass spectra of 9l
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Fig. 40.1H NMR spectra of 9m
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Fig.41. 13C NMR spectra of 9m
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Fig. 42. Mass spectrum of 9m
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Fig. 43. IR spectra of 9m
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Fig.44. HRMS spectra of 9m
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Fig. 45. 1H NMR spectra of 9n
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F N ONH
O
NF
F
Exact Mass: 373.10
Fig. 46. Mass spectrum of 9n
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Figure 47. PyMOL veiw of DNA gyrase A (PDB ID: 1ZI0)
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Figure 48. PyMOL veiw of DNA gyrase B (PDB ID: 2ZJT)
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Table 2. In vivo efficacy of quinoline acetohydrazide derivatives 9a-n for demonstrating antibacterial activity against selected pathogens