SYNTHESIS, MOLECULAR DOCKING AND ANTIBACTERIAL EVALUATION OF SOME NOVEL N-4 PIPERIDINYL DERIVATIVES OF SPARFLOXACIN
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i10.27306Keywords:
N-Piperzinyl derivatives, Ciprofloxacin, Sparfloxacin, DNA gyrase, Topoisomerase-IV, Docking studiesAbstract
Objective: The present study envisage a series of sparfloxacin derivatives were synthesized (Q1-Q10) with added derivatives such as aminomethyl benzenesulfenyl, methyl (methylamino)benzenesulfenyl, amino methyl benzoyl chloride, nitromethyl benzoyl chloride, dimethyl phenylamino, methoxymethyl phenylamino, dimethyl oxopyrazol, methyl dioxopyrrolidine, methyl oxopyrrolidine, and N-Boc amino methyl methylpyrrolidine through N-Piperzinyl linkage.
Methods: All the newly synthesized compounds were characterized by infrared,1H nuclear magnetic resonance, mass spectrometry, and elemental analysis technique, screened for docking stimulation to find out binding modes of synthesized derivatives with 3FV5 and 3IMW, and evaluated for in vitro antimicrobial activity.
Results: From this study, it was found that the compound Q5 showed good antibacterial activity against Gram-positive (Staphylococcus aureus) and compound Q4 showed good antibacterial activity against Gram-negative (Escherichia coli) in comparison with standard drugs (ciprofloxacin and sparfloxacin). The zone of inhibition and minimum inhibitory concentrations studies performed to synthesized compounds. The correlation between experimental data (minimum inhibitory concentrations) and docking score suggests that penetration for docking simulation is good to mild in reproducing experimental orientation of these synthesized compounds.
Conclusion: The analogs of sparfloxacin are suggested to be potent inhibitors with sufficient scope for further exploration.
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Hooper DC, Wolfson JS. The fluoroquinolones: Pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother 1985;28:716-21.
Ball P. Bacterial resistance to fluoroquinolones: Lessons to be learned. Infection 1994;22:140-7.
Ball PL, Mandell YN, Tilloston G. Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Saf 1999;21:407.
Ball PJ. Quinolone-induced QT interval prolongation: A not-so-unexpected class effect. J Antimicrob Chemother 2000;45:557-9.
Anderson MI, Mac Gowan AP. Development of the quinolones. J Antimicrob Chemother 2003;51 Suppl S1:1-11.
Koga H, Itoh A, Murayama S, Suzue S, Irikura T. Structure-activity relationships of antibacterial 6,7- and 7,8-disubstituted 1-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids. J Med Chem 1980;23:1358-63.
Pradip K, Ashish K, Susanta K, Swayansiddha T. Synthesis, biological evaluation, and docking studies of ciprofloxacin derivatives. Asian J Pharm Clin Res 2015;8:99-105.
Foroumadi A, Emami S, Hassanzadeh A, Rajaee M, Sokhanvar K, Moshafi MH, et al. Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives. Bioorg Med Chem Lett 2005;15:4488-92.
Domagala JM, Hanna LD, Heifetz CL, Hutt MP, Mich TF, Sanchez JP, et al. New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J Med Chem 1986;29:394-404.
Elsea SH, Osheroff N, Nitiss JL. Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast. J Biol Chem 1992;267:13150-3.
Chin NX, Gu JW, Yu KW, Zhang YK, Neu HC. In vitro activity of sparfloxacin. Antimicrob Agent Chemothe 1991;35:567-71.
Pasty BM. Clinical trial design and selected drug safety issues for antibiotics used to treat community-acquired pneumonia. Clin infect Dis Dec 2008;47:s176-9.
Shimada J, Nogita T, Ishibashi Y. Clinical pharmacokinetics of sparfloxacin. Clin Pharmacokinet 1993;25:358-69.
Nogita T, Ishibashi Y. The penetration of sparfloxacin into human plasma and skin tissues. J Antimicrob Chemother 1991;28:313-4.
Wise R, Honeybourne D. A review of the penetration of sparfloxacin into the lower respiratory tract and sinuses. J Antimicrob Chemother 1996;37 Suppl A:57-63.
Rubinstein E. Safety profile of sparfloxacin in the treatment of respiratory tract infections. J Antimicrob Chemother 1996;37 Suppl A:145-60.
Goa KL, Bryson HM, Markham A. Sparfloxacin. A review of its antibacterial activity, pharmacokinetic properties, clinical efficacy and tolerability in lower respiratory tract infections. Drugs 1997;53:700-25.
Lengauer T, Rarey M. Computational methods for biomolecular docking. Curr Opin Struct Biol 1996;6:402-6.
Ghalia S, Thanaa M. An In silico study of novel fluoroquinolones as inhibitors of DNA gyrase of Staphylococcus aureus. Int J Pharm Sci 2015;8:67-75.
Gillespie SH. Medical Microbiology Illustrated. United Kingdom: Butterworth Heinemann Ltd.; 1994. p. 234-47.
Hawkey PM, Lewis DA. Medical Bacteriology a Practical Approach. United Kingdom: Oxford University Press; 1994. p. 181-94.
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