Fe(III)-doxycycline complexes with diimine ligands: Syntheses, characterization and biological properties

Authors

  • Joshua A Obaleye Department of Chemistry, University of Ilorin, PMB 1515, Ilorin
  • Olufunso Olumide Abosede Department of Chemistry, Federal University, Otuoke, Bayelsa State

DOI:

https://doi.org/10.20450/mjcce.2019.1506

Keywords:

doxycycline, complex, diimine, synthesis, characterization biological activity

Abstract

Three new iron(III) complexes of doxycycline viz: [Fe(dox)2Cl]Cl2 (1), [Febpy(dox)Cl]Cl2 (2) and [Fephen(dox)Cl]Cl2 (3), where dox is doxycycline, bpy is 2,2ʹ-bipyridine and phen is 1,10-phenanthroline, were synthesized and characterized by elemental analysis, electronic absorption, FT-IR, and electrospray ionization mass spectroscopy. Doxycycline and the polypyridyl ligands behave as bidendate ligands; the polypyridyl ligands coordinate through the two diimine nitrogen atoms and doxycycline through enolate and diketoamide oxygen atoms of ring A in a five-coordinate system with chloride atom in the axial position. Their antibacterial and antiplasmodial activities against chloroquine-sensitive Plasmodium falciparum NF54 and their interaction with calf thymus (CT) DNA using electronic titration were investigated. The three complexes showed good activity against strains of Staphylococcus aureus and Klebsiella pneumonia. The complexes bind moderately to CT DNA with binding constants of 5.6 × 104 and 4.8 × 104 for complexes 2 and 3, respectively.

Author Biographies

Joshua A Obaleye, Department of Chemistry, University of Ilorin, PMB 1515, Ilorin

Chemistry Professor, President of American Chemical Society (Nigeria International Chapter)

Olufunso Olumide Abosede, Department of Chemistry, Federal University, Otuoke, Bayelsa State

Department of Chemistry, Lecturer

References

S. K. Roy, D. Kendrick, B. D. Sadowitz, L. Gato, K. Snyder, J. M. Satalin, L. M. Golub, G. Nieman, Jack of all trades: pleiotropy and the application of Chemically Modified Tetracycline-3 in Sepsis and the Acute Respira-tory Disease Syndrome (ARDS), Pharmacol Res., 64(6), 580–589 (2011). DOI: 10.1016/j.phrs.2011.06.012

M. O. Griffin, G. Ceballos, F. Villarreal, Tetracycline compounds with non-antimicrobial organ protective prop-erties: possible mechanisms of action, Pharmacol Res., 63(2), 102–107 (2011).

DOI: 10.1016/j.phrs.2010.10.004

M. O. Griffin, E. Fricovsky, G. Ceballos, F. Villareal, Tetracyclines: a pleiotropic family of compounds with promising therapeutic properties: Review of literature, Am J Cell Physiol, 299(3), C539–C548 (2010).

DOI: 10.1152/ajpcell.00047.2010

K. R. Tan, A. J. Magill, M. E. Parise, P. M. Arguin, Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemo-prophylaxis, Am. J Trop Med Hyg., 84(4), 517–534 (2011). DOI: 10.4269/ajtmh.2011.10-0285

T. Gaillard, M. Madamet, B. Pradines, Tetracyclines in malaria, Malar J., 14(1), 445 (2015).

DOI: 10.1186/s12936-015-0980-0

J. T. Peterson, Matrix metalloproteinase inhibitor devel-opment and the remodelling of drug discovery, Heart Fail Rev., 9(1), 63–79 (2014).

DOI:10.1023/B:HREV.0000011395.11179.af

W. Wu, L-h. Yu, B. Ma, M-j. Xu, The inhibitory effect of doxycycline on cisplatin-sensitive and –resistant epithelial ovarian cancer, PLoS ONE, 9(3) e89841 (2014). DOI: 10.1371/journal.pone.0089841

H. Tang, P. Sampath, X. Yan, S. H. Thorne, Potential for enhanced therapeutic activity of biological cancer thera-pies with doxycycline combination, Gene Ther., 20(7), 770–778 (2013). DOI: 10.1038/gt.2012.96

K. Son, S. Fujioka, T. Iida, K. Furukawa, T. Fujita, H. Yamada, P. J. Chiao, K. Yanaga, Doxycycline induces apoptosis in PANC-1 pancreatic cancer cells, Anticancer Res., 29(10), 3995–4003 (2009).

Z. Saikali, G. Singh, Doxycycline and other tetracyclines in the treatment of bone metastasis, Anticancer Drugs, 14(10), 773–778 (2003).

DOI:10.1097/01.cad.0000099002.92896.cf

M. E. Ryan, A. Usman, N. S. Ramamurthy, L. M. Golub, R. A. Greenwald, Excessive matrix metalloproteinase ac-tivity in diabetes: Inhibition by tetracycline analogues with zinc reactivity, Curr Med Chem., 8(3), 305–316 (2001). DOI: 10.2174/0929867013373598

L. M. Golub, N. S. Ramamurthy, T. F. McNamara, R. A. Greenwald, B. R. Rifkin, Tetracyclines inhibit connective tissue breakdown: New therapeutic implications for an old family of drugs, Crit Rev Oral Biol Med., 2, 297–321 (1991).

DOI: https://doi.org/10.1177/10454411910020030201

L. M. Golub, H. M. Lee, M. E. Ryan, W. V. Giannobile, J. Payne and T. Sorsa, Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mecha-nisms, Adv Dent Res., 12, 12–26 (1998).

DOI: https://doi.org/10.1177/08959374980120010501

M. A. Khan, J. Mustafa, Mechanism of DNA strand breakage induced by photosensitized tetracycline–Cu(II) complex, Mutation Research, 525, 109–119 (2003). DOI: 10.1016/S0027-5107(03)00008-3

P. P. Silva, W. Guerra, J. N. Silveira, A. M. C. Ferreira, T. Bortolotto, F. L. Fischer, H. Terenzi, A. Neves, E. C. Pereira-Maia, Two new ternary complexes of copper(II) with tetracycline or doxycycline and 1,10-phenanthroline and their potential as antitumoral: cytotoxicity and DNA cleavage, Inorg. Chem., 50 (14), 6414–6424 (2011). DOI: 10.1021/ic101791r

T. Bortolotto, P. P. Silva, A. Neves, E. C. Pereira-Maia, H. Terenzi, Photoinduced DNA cleavage promoted by two copper(II) complexes of tetracyclines and 1,10-phenanthroline, Inorg. Chem., 50 (21), 10519–10521 (2011). DOI: 10.1021/ic201349s

W. W. Brandt, F. P. Dwyer, E. C. Gyarfas, Chelate com-plexes of 1,10-phenanthroline and related compounds, Chemical Reviews, 54, 959–1017 (1954). DOI: 10.1021/cr60172a003

M. McCann, M. Geraghty, M. Devereux, D. O’Shea, J. Mason, L. O'Sullivan, Insights into the mode of action of the anti-Candida activity of 1,10-phenanthroline and its metal chelates, Metal Based Drugs, 7(4), 185–193 (2000). DOI: 10.1155/MBD.2000.185

L. Salassa, Polypyridyl Metal Complexes with biological activity, Eur. J. Inorg. Chem., 32, 4931–4947 (2011). DOI: https://doi.org/10.1002/ejic.201100376

E. C. Constable, Homoleptic complexes of 2,2’-bipyridine, Adv. Inorg. Chem., 34, 1–63 (1989).

DOI: https://doi.org/10.1016/S0898-8838(08)60014-8

G. Chelucci, R. P. Thummel, Chiral 2,2‘-bipyridines, 1,10-phenanthrolines, and 2,2‘:6‘,2‘ ‘-terpyridines: Syn-theses and applications in asymmetric homogeneous ca-talysis, Chem. Rev., 102(9), 3129–3170 (2002).

DOI: 10.1021/cr0101914

N. Mudasir, H. I. Yoshioka, Iron(II) and nickel(II) mixed-ligand complexes containing 1,10-phenanthroline and 4,7-diphenyl-1,10-phenanthroline, Transition Met. Chem., 24(2), 210–217 (1999).

DOI: 10.1016/S0162-0134(99)00206-8

M. Riaz, N. J. Pilpel, Complexation of tetracyclines with metal ions in relation to photosensitization, Pharm. Pharmacol., 36, 153–156 (1984).

DOI: https://doi.org/10.1111/j.2042-7158.1984.tb06929.x

D. Grenier, M-P. Huot, D. Mayr, Iron-chelating activity of tetracyclines and its impact on the susceptibility of Actinobacillus actinomycetemcomitans to these antibi-otics, Antimicrob. Agents Chemother., 44, 763–766 (2000).

S. Saha, D. Mallick, R. Majumdar, M. Roy, R. R. Dighe, E. D. Jemmis, A. R. Chakravarty, Structure-activity rela-tionship of photocytotoxic iron(III) complexes of modi-fied dipyridophenazine ligands, Inorg. Chem., 50(7), 2975–2985 (2011). DOI: 10.1021/ic1024229

A. Terenzi, G. Barone, A. Silvestri, A. M. Giuliani, A. Ruggirello, V. T. Liveri, The interaction of native calf thymus DNA with FeIII-dipyrido[3,2-a: 2′,3′-c]phena–zine, J. Inorg. Biochem, 103, 1–9 (2009).

DOI: 10.1016/j.jinorgbio.2008.08.011

G. M. Keating, Ferric carboxymaltose: a review of its use in iron-deficiency, Drugs, 75(1), 101–127 (2015). DOI: 10.1007/s40265-014-0332-3

I. C. Macdougall, Evolution of IV iron compounds over the last century, J Ren Care., 35(2), 8–13 (2009).

DOI: 10.1111/j.1755-6686.2009.00127.x

P. Ponikowski, D. J. van Veldhuisen, J. Comin-Colet, G. Ertl, M. Komajda, V. Mareev, T. McDonagh, A. Par-khomenko, L. Tavazzi, V. Levesque, C. Mori, B. Rou-bert, G. Filippatos, F. Ruschitzka, S. D. Anker, Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency, European Heart Journal, 36(11), 657–668 (2014). DOI: 10.1093/eurheartj/ehu385

J A. Obaleye, A. C. Tella, W. A. Osunniran, N. Simon, P. F. Omojasola, Synthesis, characterization, crystal structure and antimicrobial evaluation of a novel –M–X–M–X– type infinite chain 1D Cu(II) complex with eflornithine hydrochloride hydrate as ligand, J. Inorg and Organomet Polymer Mater, 24(5), 827–835 (2014). DOI: https://doi.org/10.1007/s10904-014-0052-x

O. O. Abosede, N. A. Vyas, S. B. Singh, A. Kumbhar, A. N. Kate, A. A. Kumbhar, A. Khan, A. Erxleben, P. Smith, C. de Kock, F. Hoffmann, J. Obaleye, Copper(II) mixed ligand polypyridyl complexes with doxycycline - structures and biological evaluation, Dalton Trans., 45, 3003–3012 (2016).

DOI: 10.1039/c5dt04405g

A. C. Tella, J. A. Obaleye, U. B. Eke, A.Y. Isaac, O. M. Ameen, Solvent-free synthesis, X-ray studies and in vitro inhibitory activities of copper(II) complexes of non-steroidal anti-inflammatory drugs, Res. Chem. Interm. 40, 1441–1457 (2014).

DOI: https://doi.org/10.1007/s11164-013-1050-2

J. A. Obaleye, O. O. Abosede, A. S. Kumbhar, O. A. Majolagbe, Syntheses, characterization and antibacterial susceptibility testing of transition metal complexes of doxycycline, Can Chem Trans., 4(2), 168–179 (2016). DOI:10.13179/canchemtrans.2016.04.02.0257

M. Cheesbrough, District Laboratory Practice in Tropi-cal Countries, Part 2, Cambridge University Press, Cam-bridge, UK, 2006, p. 137–150.

W. Trager, J. B. Jensen, Human malaria parasite in con-tinuous culture, Science, 193, 673–675 (1976).

DOI: 10.1126/science.781840

M. T. Makler, J. M. Ries, J. A. Williams, J. E. Bancroft, R. C. Piper, B. L. Gibbins and D. J. Hinrichs, Parasite lactate dehydrogenase as an assay for Plasmodium falci-parum drug sensitivity, Am. J. Trop. Med. Hyg., 48, 739–741 (1993). DOI: https://doi.org/10.4269/ajtmh.1993.48.739

V. A. Kawade, A. A. Kumbhar, A. S. Kumbhar, C. Nather, A. Erxleben, U. B. Sonawane, R. R. Joshi, Mixed ligand cobalt(II) picolinate complexes: synthesis, characterization, DNA binding and photocleavage, Dalton Trans., 40, 639–650 (2011). DOI: 10.1039/c0dt01078b

S. S. Bhat, A. A. Kumbhar, H. Heptullah, A. A. Khan, V. V. Gobre, S. P. Gejji, V. G. Puranik, Synthesis, electron-ic structure, DNA and protein binding, DNA cleavage, and anticancer activity of fluorophore-labeled copper(II) complexes, Inorg. Chem., 50, 545–558 (2011). DOI: 10.1021/ic101534n

C. V. Kuman. E. H. Asuncion, DNA-binding studies and site-selective fluorescence sensitization of an anthryl probe, J. Am. Chem. Soc., 115, 8547–8553 (1993). DOI: 10.1021/ja00072a004

A. Wolfe, G. H. Shimer, T. Meehan, Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA, Biochemistry, 26, 6392–6396 (1987). DOI: 10.1021/bi00394a013

T.G. Emori, R. P. Gaynes, An overview of nosocomial infections, including the role of the microbiology labora-tory, Clin. Microbiol. Rev., 6, 428–442 (1993).

DOI: 10.1128/CMR.6.4.428

K. Shameli, M. B. Ahmad, M. Zargar, W. M. Z. W. Yunus, A. Rustaiyan, N. A. Ibrahim, Synthesis of silver nanoparticles in montmorillonite and their antibacterial behavior, International Journal of Nanomedicine, 6, 581–590 (2011). DOI: 10.2147/IJN.S17112

S. M. Sivakumar, M. M. Safhi, Isolation and screening of bioactive principle from Chaetomorpha antennina against certain bacterial strains, Saudi Pharmaceutical Journal, 21, 119–121 (2013).

DOI: 10.1016/j.jsps.2012.02.003

B. Pradines, C. Rogier, T. Fusai, J. Mosnier, W. Daries, E. Barret, D. Parzy, In vitro activities of antibiotics against Plasmodium falciparum are inhibited by iron, An-timicrob. Agents Chemother., 45, 17460–1750 (2001). DOI: 10.1128/AAC.45.6.1746-1750.2001

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Published

2019-05-24

How to Cite

Obaleye, J. A., & Abosede, O. O. (2019). Fe(III)-doxycycline complexes with diimine ligands: Syntheses, characterization and biological properties. Macedonian Journal of Chemistry and Chemical Engineering, 38(1), 29–38. https://doi.org/10.20450/mjcce.2019.1506

Issue

Vol. 38 No. 1 (2019)

Section

Inorganic Chemistry

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