Four new metal complexes (S12–S15) of SPFX (third-generation quinolones) via heavy metals have been synthesized in good yield and characterized by physicochemical and spectroscopic methods including TLC, IR, NMR, and elemental analyses. Sparfloxacinato ligand binds with metals through pyridone and oxygen atom of carboxylic group. The biological actives of complexes have been tested against four Gram-positive and seven Gram-negative bacteria and six different fungi. Statistical analysis of antimicrobial data was done by one-way ANOVA, Dunnett’s test; it was observed that S13, S14, and S15 were found to be most active complexes. Antifungal data confirm that all four synthesized complexes are most active and show significant activity against F. solani with respect to parent drug and none of complexes show activity against A. parasiticus, A. effuris, and S. cervicis. To study inhibitory effects of newly formed complexes, enzyme inhibition studies have been conducted against urease, α-chymotrypsin, and carbonic anhydrase. Enzymatic activity results of these complexes indicated them to be good inhibitors of urease enzyme while all complexes show mild activities against carbonic anhydrase enzyme. Further research may prove the promising role of these synthesized complexes as urease inhibitors. 1. Introduction For infectious diseases, multiple therapies are usually required and so the possibility of drug-drug interactions increased. Careful consideration of concomitant drug therapy is needed. Literature survey reveals that fluoroquinolones showed several important interactions with many drugs [1]. Usually fluoroquinolones are prescribed for many diseases including respiratory and urinary tract infections. Sparfloxacin (SPFX) is an orally active synthetically broadspectrum third-generation quinolones use for upper respiratory tract infection. Metals are considered essential to a human body in performing physiologically important and vital functions, in the body [2]. The action of many drugs is dependent on coordination with metal ions or/and the inhibition on the formation of metalloenzymes [3]. The proposed mechanism of the interaction is chelation between the 4-oxo and adjacent carboxyl group of quinolone and metal cations [4–8]. Literature survey reveals that concurrent administration of magnesium and aluminium containing antacid with ciprofloxacin resulted in a nearly complete loss of activity of the drug [9] and patients who orally administrated fluoroquinolones should avoid mixtures containing multivalent cations, because quinolones binds with these metals
References
[1]
J. Kang, L. Wang, X.-L. Chen, D. J. Triggle, and D. Rampe, “Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG,” Molecular Pharmacology, vol. 59, no. 1, pp. 122–126, 2001.
[2]
W. Mertz, “Review of the scientific basis for establishing the essentiality of trace elements,” Biological Trace Element Research, vol. 66, no. 1–3, pp. 185–191, 1998.
[3]
E. K. Efthimiadou, Y. Sanakis, N. Katsaros, A. Karaliota, and G. Psomas, “Transition metal complexes with the quinolone antibacterial agent pipemidic acid: synthesis, characterization and biological activity,” Polyhedron, vol. 26, no. 5, pp. 1148–1158, 2007.
[4]
M. S. Arayne, N. Sultana, and F. Hussain, “In vitro monitoring of ciprofloxacin antacids interactions by UV & HPLC,” Pakistan Journal of Pharmaceutical Sciences, vol. 18, no. 4, pp. 23–31, 2005.
[5]
J. Al-Mustafa, “Magnesium, calcium and barium perchlorate complexes of ciprofloxacin and norfloxacin,” Acta Chimica Slovenica, vol. 49, no. 3, pp. 457–466, 2002.
[6]
S. Sagdinca and S. Bayaryb, “Spectroscopic studies on the interaction of ofloxacin with metals,” Journal of Molecular Structure, vol. 691, no. 1–3, pp. 107–113, 2004.
[7]
I. Turel, “The interactions of metal ions with quinolone antibacterial agents,” Coordination Chemistry Reviews, vol. 232, no. 1-2, pp. 27–47, 2002.
[8]
B. Macías, M. V. Villa, I. Rubio, A. Casti？eiras, and J. Borrás, “Complexes of Ni(II) and Cu(II) with ofloxacin: crystal structure of a new Cu(II) ofloxacin complex,” Journal of Inorganic Biochemistry, vol. 84, no. 3-4, pp. 163–170, 2001.
[9]
N. Sultana, M. S. Arayne, S. Gul, and S. Shamim, “Sparfloxacin-metal complexes as antifungal agents—their synthesis, characterization and antimicrobial activities,” Journal of Molecular Structure, vol. 975, no. 1–3, pp. 285–291, 2010.
[10]
G. Hoffken, K. Borner, P. D. Glatzel, P. Koeppe, and H. Lode, “Reduced enteral absorption of ciprofloxacin in the presence of antacids,” European Journal of Clinical Microbiology, vol. 4, no. 3, p. 345, 1985.
[11]
H. H. M. Ma, F. C. K. Chiu, and R. C. Li, “Mechanistic investigation of the reduction in antimicrobial activity of ciprofloxacin by metal cations,” Pharmaceutical Research, vol. 14, no. 3, pp. 366–370, 1997.
[12]
H. N. Alkaysi, M. H. Abdel-Hay, M. Sheikh Salem, A. M. Gharaibeh, and T. E. Na'was, “Chemical and microbiological investigations of metal ion interaction with norfloxacin,” International Journal of Pharmaceutics, vol. 87, no. 1–3, pp. 73–77, 1992.
[13]
E. K. Efthimiadou, A. Karaliota, and G. Psomas, “Mononuclear dioxomolybdenum(VI) complexes with the quinolones enrofloxacin and sparfloxacin: synthesis, structure, antibacterial activity and interaction with DNA,” Polyhedron, vol. 27, no. 1, pp. 349–356, 2008.
[14]
E. K. Efthimiadou, Y. Sanakis, N. Katsaros, A. Karaliota, and G. Psomas, “Transition metal complexes with the quinolone antibacterial agent pipemidic acid: synthesis, characterization and biological activity,” Polyhedron, vol. 26, no. 5, pp. 1148–1158, 2007.
[15]
E. K. Efthimiadou, Y. Sanakis, C. P. Raptopoulou, A. Karaliota, N. Katsaros, and G. Psomas, “Crystal structure, spectroscopic, and biological study of the copper(II) complex with third-generation quinolone antibiotic sparfloxacin,” Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 14, pp. 3864–3867, 2006.
[16]
E. K. Efthimiadou, M. E. Katsarou, A. Karaliota, and G. Psomas, “Copper(II) complexes with sparfloxacin and nitrogen-donor heterocyclic ligands: structure-activity relationship,” Journal of Inorganic Biochemistry, vol. 102, no. 4, pp. 910–920, 2008.
[17]
K. C. Skyrianou, E. K. Efthimiadou, V. Psycharis, A. Terzis, D. P. Kessissoglou, and G. Psomas, “Nickel-quinolones interaction—part 1: nickel(II) complexes with the antibacterial drug sparfloxacin: structure and biological properties,” Journal of Inorganic Biochemistry, vol. 103, no. 12, pp. 1617–1625, 2009.
[18]
G. Psomas, “Mononuclear metal complexes with ciprofloxacin: synthesis, characterization and DNA-binding properties,” Journal of Inorganic Biochemistry, vol. 102, no. 9, pp. 1798–1811, 2008.
[19]
H. N. Alkaysi, M. H. Abdel-Hay, M. Sheikh Salem, A. M. Gharaibeh, and T. E. Na'was, “Chemical and microbiological investigations of metal ion interaction with norfloxacin,” International Journal of Pharmaceutics, vol. 87, no. 1–3, pp. 73–77, 1992.
[20]
I. Turel, “The interactions of metal ions with quinolone antibacterial agents,” Coordination Chemistry Reviews, vol. 232, no. 1-2, pp. 27–47, 2002.
[21]
I. Turel, I. Leban, and N. Bukovec, “Synthesis, characterization, and crystal structure of a copper(II) complex with quinolone family member (ciprofloxacin): bis(1-cyclopropyl-6-fluoro- 1,4-dihydro-4-oxo-7-piperazin-1ylquinoline-3-carboxylate) copper(II) chloride hexahydrate,” Journal of Inorganic Biochemistry, vol. 56, no. 4, pp. 273–282, 1994.
[22]
I. Turel, K. Gruber, I. Leban, and N. Bukovec, “Synthesis, crystal structure, and characterization of three novel compounds of the quinolone family member (norfloxacin),” Journal of Inorganic Biochemistry, vol. 61, no. 3, pp. 197–212, 1996.
[23]
S. C. Wallis, L. R. Gahan, B. G. Charles, and T. W. Hambley, “Synthesis and X-ray structural characterization of an iron(III) complex of the fluoroquinolone antimicrobial ciprofloxacin,” Polyhedron, vol. 14, no. 20-21, pp. 2835–2840, 1995.
[24]
S. C. Wallis, L. R. Gahan, B. G. Charles, T. W. Hambley, and P. A. Duckworth, “Copper(II) complexes of the fluoroquinolone antimicrobial ciprofloxacin. Synthesis, X-ray structural characterization, and potentiometric study,” Journal of Inorganic Biochemistry, vol. 62, no. 1, pp. 1–16, 1996.
[25]
Z.-F. Chen, R.-G. Xiong, J. Zhang, X.-T. Chen, Z.-L. Xue, and X.-Z. You, “2D molecular square grid with strong blue fluorescent emission: a complex of norfloxacin with zinc(II),” Inorganic Chemistry, vol. 40, no. 16, pp. 4075–4077, 2001.
[26]
B. Macías, M. V. Villa, I. Rubio, A. Casti？eiras, and J. Borrás, “Complexes of Ni(II) and Cu(II) with ofloxacin: crystal structure of a new Cu(II) ofloxacin complex,” Journal of Inorganic Biochemistry, vol. 84, no. 3-4, pp. 163–170, 2001.
[27]
L.-Z. Wang, Z.-F. Chen, X.-S. Wang, Y.-H. Li, R.-G. Xiong, and X.-Z. You, “2D nanoporous molecular square grid: manganese (II) norfloxacin complex,” Chinese Journal of Inorganic Chemistry, vol. 18, no. 12, pp. 1185–1190, 2002.
[28]
M. S. Arayne, N. Sultana, and F. Hussain, “Interactions between sparfloxacin and antacids: dissolution and adsorption studies,” Pakistan Journal of Pharmaceutical Sciences, vol. 19, no. 1, pp. 16–21, 2006.
[29]
S. Arayne, N. Sultana, U. Haroon, and M. A. Mesaik, “Synthesis, characterization, antibacterial and anti-inflammatory activities of enoxacin metal complexes,” Bioinorganic Chemistry and Applications, vol. 2009, Article ID 914105, 6 pages, 2009.
[30]
N. Sultana, A. Naz, M. S. Arayne, and M. A. Mesaik, “Synthesis, characterization, antibacterial, antifungal and immunomodulating activities of gatifloxacin-metal complexes,” Journal of Molecular Structure, vol. 969, no. 1–3, pp. 17–24, 2010.
[31]
A. W. Bauer, W. M. Kirby, J. C. Sherris, and M. Turck, “Antibiotic susceptibility testing by a standardized single disk method,” The American Journal of Clinical Pathology, vol. 45, no. 4, pp. 493–496, 1966.
[32]
National Committee on Clinical Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility Tests, NCCLS, Villanova, Pa, USA, 1983.
[33]
LMD Victor Antibiotics in Laboratory Medicine, Williams and Wilkins, 3rd edition, 1991.
[34]
E. K. Efthimiadou, A. Karaliota, and G. Psomas, “Structure, antimicrobial activity and DNA-binding properties of the cobalt(II)-sparfloxacin complex,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 14, pp. 4033–4037, 2008.
[35]
E. K. Efthimiadou, Y. Sanakis, C. P. Raptopoulou, A. Karaliota, N. Katsaros, and G. Psomas, “Crystal structure, spectroscopic, and biological study of the copper(II) complex with third-generation quinolone antibiotic sparfloxacin,” Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 14, pp. 3864–3867, 2006.
[36]
E. K. Efthimiadou, M. E. Katsarou, A. Karaliota, and G. Psomas, “Copper(II) complexes with sparfloxacin and nitrogen-donor heterocyclic ligands: structure-activity relationship,” Journal of Inorganic Biochemistry, vol. 102, no. 4, pp. 910–920, 2008.
[37]
S. Jain, N. K. Jain, and K. S. Pitre, “Bio-inorganic studies on the Fe(II) sparfloxacin complex,” Metal-Based Drugs, vol. 9, no. 1-2, pp. 1–8, 2002.
[38]
E. Prestch, T. Clerc, J. Seibl, and W. Simon, Tablas de Determinacion Estructural Por Metodos Espectroscopicos, Springer, Barcelona, Spain, 1998.
[39]
N. Jiménez-Garrido, L. Perelló, R. Ortiz et al., “Antibacterial studies, DNA oxidative cleavage, and crystal structures of Cu(II) and Co(II) complexes with two quinolone family members, ciprofloxacin and enoxacin,” Journal of Inorganic Biochemistry, vol. 99, no. 3, pp. 677–689, 2005.
[40]
M. Saeed Arayne, N. Sultana, and A. Zeeshan Mirza, “Preparation and spectroscopic characterization of metal complexes of gliquidone,” Journal of Molecular Structure, vol. 927, no. 1-3, pp. 54–59, 2009.
