Synthesis, characterization and antibacterial study of Co(II) and Cu(II) complexes of mixed ligands of piperaquine and diclofenac

Year 2021, Volume: 8 Issue: 2, 633 - 650, 31.05.2021

Yusuf Ayipo , Wahab Osunniran Umar Badeggi Ismaila Saheed Akeem Jımoh , Halimah Babamale

https://doi.org/10.18596/jotcsa.898523

Cited By: 1

Abstract

Pathogenic microorganisms develop incessant resistance toward antibiotics through various cellular defense mechanisms, thereby creating a search for chemotherapeutic alternatives, the potentials of which metal complexes of small-molecule drugs offer. In this study, Cu(II) and Co(II) complexes of mixed piperaquine and diclofenac were synthesized and characterized via magnetic moment determination, elemental analysis, FTIR, UV-Visible, 1D 1H NMR, 13C NMR spectroscopy and powder XRD, then evaluated for biological activities in silico and in vitro. The results provide evidence of coordination of the metal ions to ligands through N, COO and Cl groups with proposed octahedral geometry, low spin, paramagnetic, polycrystalline complexes. The physicochemical and pharmacokinetic parameters predicted in silico support bio-functionality and safety of the complexes. The complexes demonstrate strong inhibition against bacterial strains especially Staphylococcus aureus in vitro. Specifically, Cu(II) complex at 1% w/w inhibited a zone of 100 mm which is in multi-folds of the effects of piperaquine and diclofenac with 32 and 25 mm respectively, and better than ciprofloxacin with 92 mm. On DPPH assay, both complexes display better antioxidant potentials with respective IC50 of 165.09 and 382.7 µg/mL compared to ascorbic acid with 7526 µg/mL. Thus, the complexes represent therapeutic models for overcoming antibacterial resistance upon further study.

Keywords

Antibiotic resistance, bioinorganic, spectroscopy, powder XRD, biological study

Supporting Institution

Tertiary Education Fund

Thanks

The authors wish to acknowledge the Tetfund Nigeria for PhD scholarship awarded to YOA.

References

• 1. Naglah AM, Al-Omar MA, Almehizia AA, AlKahtani HM, Bhat MA, Al-Shakliah NS, et al. Synthesis, thermogravimetric, and spectroscopic characterizations of three palladium metal(II) ofloxacin drug and amino acids mixed ligand complexes as advanced antimicrobial materials. Journal of Molecular Structure. 2021 Feb;1225:129102. DOI: https://doi.org/10.1016/j.molstruc.2020.129102.
• 2. Mohamed GG, El-Sherif AA, Saad MA, El-Sawy SEA, Morgan ShM. Mixed-ligand complex formation of tenoxicam drug with some transition metal ions in presence of valine: Synthesis, characterization, molecular docking, potentiometric and evaluation of the humeral immune response of calves. Journal of Molecular Liquids. 2016 Nov;223:1311–32. DOI: https://doi.org/10.1016/j.molliq.2016.09.065.
• 3. Bergamo A, Dyson PJ, Sava G. The mechanism of tumour cell death by metal-based anticancer drugs is not only a matter of DNA interactions. Coordination Chemistry Reviews. 2018 Apr;360:17–33. DOI: https://doi.org/10.1016/j.ccr.2018.01.009.
• 4. Boros E, Dyson PJ, Gasser G. Classification of Metal-Based Drugs according to Their Mechanisms of Action. Chem. 2020 Jan;6(1):41–60. DOI: https://doi.org/10.1016/j.chempr.2019.10.013.
• 5. Schmidt C, Karge B, Misgeld R, Prokop A, Franke R, Brönstrup M, et al. Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of Mammalian and Bacterial Thioredoxin Reductases, and Gram-Positive Directed Antibacterial Effects. Chem Eur J. 2017 Feb 3;23(8):1869–80. DOI: https://doi.org/10.1002/chem.201604512.
• 6. Zhou G, Shi Q-S, Huang X-M, Xie X-B. The Three Bacterial Lines of Defense against Antimicrobial Agents. IJMS. 2015 Sep 9;16(9):21711–33. DOI: https://doi.org/10.3390/ijms160921711.
• 7. Paladini F, Pollini M, Sannino A, Ambrosio L. Metal-Based Antibacterial Substrates for Biomedical Applications. Biomacromolecules. 2015 Jul 13;16(7):1873–85. DOI: https://doi.org/10.1021/acs.biomac.5b00773.
• 8. Alven S, Aderibigbe BA, Balogun MO, Matshe WMR, Ray SS. Polymer-drug conjugates containing antimalarial drugs and antibiotics. Journal of Drug Delivery Science and Technology. 2019 Oct;53:101171. DOI: https://doi.org/10.1016/j.jddst.2019.101171.
• 9. Turner RJ. Metal-based antimicrobial strategies. Microb Biotechnol. 2017 Sep;10(5):1062–5. DOI: https://doi.org/10.1111/1751-7915.12785.
• 10. Fiori ATM, Nakahata DH, Cuin A, Lustri WR, Corbi PP. Synthesis, crystallographic studies, high resolution mass spectrometric analyses and antibacterial assays of silver(I) complexes with sulfisoxazole and sulfadimethoxine. Polyhedron. 2017 Jan;121:172–9. DOI: https://doi.org/10.1016/j.poly.2016.09.046.
• 11. Divya K, Narayana B, Samshuddin S. New spectrophotometric methods for the determination of sulfadoxine by the formation of Co(II) complexes. Journal of Saudi Chemical Society. 2016 Sep;20:S536–40. DOI: https://doi.org/10.1016/j.jscs.2013.03.011.
• 12. K. O. Ogunniran. Cu(II) and Fe(III) complexes of sulphadoxine mixed with pyramethamine: Synthesis, characterization, antimicrobial and toxicology study. Int J Phys Sci [Internet]. 2012 Mar 23 [cited 2021 May 3];7(13). Available from: http://www.academicjournals.org/IJPS/abstracts/abstracts/abstract2012/23Mar/Ogunniran%20et%20al.htm
• 13. Hu Y-Q, Gao C, Zhang S, Xu L, Xu Z, Feng L-S, et al. Quinoline hybrids and their antiplasmodial and antimalarial activities. European Journal of Medicinal Chemistry. 2017 Oct;139:22–47. DOI: https://doi.org/10.1016/j.ejmech.2017.07.061.
• 14. Idemudia O, Sadimenko A, Hosten E. Metal Complexes of New Bioactive Pyrazolone Phenylhydrazones; Crystal Structure of 4-Acetyl-3-methyl-1-phenyl-2-pyrazoline-5-one phenylhydrazone Ampp-Ph. IJMS. 2016 May 18;17(5):687. DOI: https://doi.org/10.3390/ijms17050687.
• 15. Kakoulidou C, Gritzapis PS, Hatzidimitriou AG, Fylaktakidou KC, Psomas G. Zn(II) complexes of (E)-4-(2-(pyridin-2-ylmethylene)hydrazinyl)quinazoline in combination with non-steroidal anti-inflammatory drug sodium diclofenac: Structure, DNA binding and photo-cleavage studies, antioxidant activity and interaction with albumin. Journal of Inorganic Biochemistry. 2020 Oct;211:111194. DOI: https://doi.org/10.1016/j.jinorgbio.2020.111194.
• 16. Ayipo YO, Obaleye JA, Badeggi UM. Novel metal complexes of mixed piperaquine-acetaminophen and piperaquine-acetylsalicylic acid: Synthesis, characterization and antimicrobial activities. Journal of the Turkish Chemical Society, Section A: Chemistry. 2016 Nov 11;4(1):313–313. DOI: https://doi.org/10.18596/jotcsa.287331.
• 17. Okasha RM, AL-Shaikh NE, Aljohani FS, Naqvi A, Ismail EH. Design of Novel Oligomeric Mixed Ligand Complexes: Preparation, Biological Applications and the First Example of Their Nanosized Scale. IJMS. 2019 Feb 10;20(3):743. DOI: https://doi.org/10.3390/ijms20030743.
• 18. Syed Ali Fathima S, Paulpandiyan R, Nagarajan ER. Expatiating biological excellence of aminoantipyrine derived novel metal complexes: Combined DNA interaction, antimicrobial, free radical scavenging studies and molecular docking simulations. Journal of Molecular Structure. 2019 Feb;1178:179–91. DOI: https://doi.org/10.1016/j.molstruc.2018.10.021.
• 19. Bunaciu AA, Udriştioiu E gabriela, Aboul-Enein HY. X-Ray Diffraction: Instrumentation and Applications. Critical Reviews in Analytical Chemistry. 2015 Oct 2;45(4):289–99. DOI: https://doi.org/10.1080/10408347.2014.949616.
• 20. Dorset DL. Crystal Structure Analysis. In: Structural Electron Crystallography [Internet]. Boston, MA: Springer US; 1995 [cited 2021 May 3]. p. 95–133. Available from: http://link.springer.com/10.1007/978-1-4757-6621-9_4.
• 21. Holder CF, Schaak RE. Tutorial on Powder X-ray Diffraction for Characterizing Nanoscale Materials. ACS Nano. 2019 Jul 23;13(7):7359–65. DOI: https://doi.org/10.1021/acsnano.9b05157.
• 22. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017 May;7(1):42717. DOI: https://doi.org/10.1038/srep42717.
• 23. Limbago B. M100-S11, Performance standards for antimicrobial susceptibility testing. Clinical Microbiology Newsletter. 2001 Mar;23(6):49. DOI: https://doi.org/10.1016/S0196-4399(01)88009-0.
• 24. Nichols L. 6.1C: Melting Point Theory [Internet]. Chemistry LibreTexts; 2020. Available from: https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_Lab_Techniques_(Nichols)/06%3A_Miscellaneous_Techniques/6.01%3A_Melting_Point/6.1C%3A__Melting_Point_Theory
• 25. Refat MS, Mohamed GG, Ibrahim MYS, Killa HMA, Fetooh H. Synthesis and Characterization of Coordination Behavior of Diclofenac Sodium Drug Toward Hg(II), Pb(II), and Sn(II) Metal Ions: Chelation Effect on Their Thermal Stability and Biological Activity. Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry. 2014 Feb 7;44(2):161–70. https://doi.org/10.1080/15533174.2012.752009.
• 26. Perontsis S, Dimitriou A, Fotiadou P, Hatzidimitriou AG, Papadopoulos AN, Psomas G. Cobalt(II) complexes with the non-steroidal anti-inflammatory drug diclofenac and nitrogen-donor ligands. Journal of Inorganic Biochemistry. 2019 Jul;196:110688. DOI: https://doi.org/10.1016/j.jinorgbio.2019.04.002.
• 27. Osunniran W, Obaleye J, Ayipo Y, Rajee A, Enemose E. Six Coordinate Transition Metal (II) Complexes of Mixed Ligands of Eflornithine Hydrochloride Hydrate and 2,2-Bipyridine: Synthesis, Characterization and Antibacterial Study. Jordan J Chem. 2018;13(3):149–57. URL: http://jjc.yu.edu.jo/index.php/jjc/article/view/39.
• 28. Al-Adilee K, Dakheel H. Synthesis, Spectral and Biological Studies of Ni(II), Pd(II), and Pt(IV) Complexes with New Heterocyclic ligand Derived from Azo-Schiff Bases Dye. Eurasian J Anal Chem [Internet]. 2018 Oct 2 [cited 2021 May 3];13(6). Available from: http://www.journalssystem.com/ejac/,97267,0,2.html
• 29. Lakshmi S, Endo T, Siva G. Electronic (Absorption) Spectra of 3d Transition Metal Complexes. In: Akhyar Farrukh M, editor. Advanced Aspects of Spectroscopy [Internet]. InTech; 2012 [cited 2021 May 3]. Available from: http://www.intechopen.com/books/advanced-aspects-of-spectroscopy/electronic-absorption-spectra-of-3d-transition-metal-complexes
• 30. Radoń M, Rejmak P, Fitta M, Bałanda M, Szklarzewicz J. How can [Mo IV (CN) 6 ] 2− , an apparently octahedral (d) 2 complex, be diamagnetic? Insights from quantum chemical calculations and magnetic susceptibility measurements. Phys Chem Chem Phys. 2015;17(22):14890–902. DOI: https://doi.org/10.1039/C4CP04863F.
• 31. Salazar-Medina AJ, Gámez-Corrales R, Ramírez JZ, González-Aguilar GA, Velázquez-Contreras EF. Characterization of metal-bound water in bioactive Fe(III)-cyclophane complexes. Journal of Molecular Structure. 2018 Feb;1154:225–31. DOI: https://doi.org/10.1016/j.molstruc.2017.10.018.
• 32. Xu X-H, Kuang M-Q. Interpretation of the Electron Paramagnetic Resonance Spectra of Copper(II)–Tyrosine Complex. Zeitschrift für Naturforschung A. 2017 Dec 20;73(1):75–8. DOI: https://doi.org/10.1515/zna-2017-0239.
• 33. Ott JC, Wadepohl H, Enders M, Gade LH. Taking Solution Proton NMR to Its Extreme: Prediction and Detection of a Hydride Resonance in an Intermediate-Spin Iron Complex. J Am Chem Soc. 2018 Dec 19;140(50):17413–7. DOI: https://doi.org/10.1021/jacs.8b11330.
• 34. Müntener T, Böhm R, Atz K, Häussinger D, Hiller S. NMR pseudocontact shifts in a symmetric protein homotrimer. J Biomol NMR. 2020 Sep;74(8–9):413–9. DOI: https://doi.org/10.1007/s10858-020-00329-7.
• 35. Ramotowska S, Wysocka M, Brzeski J, Chylewska A, Makowski M. A comprehensive approach to the analysis of antibiotic-metal complexes. TrAC Trends in Analytical Chemistry. 2020 Feb;123:115771. DOI: https://doi.org/10.1016/j.trac.2019.115771.
• 36. Speakman S. Basics of X-Ray Powder Diffraction [Internet]. MIT; 2018. Available from: http://prism.mit.edu/xray.
• 37. Wang Q, Huang YM, Ma XL, Li SS, Li H. X-ray powder diffraction data for piperaquine, C 29 H 32 Cl 2 N 6. Powder Diffr. 2015 Sep;30(3):289–92. DOI: https://doi.org/10.1017/S0885715615000524.
• 38. Ibragimov A, Ashurov J, Dusmatov A, Ibragimov A. Crystal structure and Hirshfeld surface analysis of the orthorhombic polymorph of a Zn II complex with 3,5-dinitrobenzoic acid and ethylenediamine. Acta Crystallogr E Cryst Commun. 2020 Jul 1;76(7):1113–6. DOI: https://doi.org/10.1107/S2056989020007938.
• 39. Marino SF, Regan L. Secondary ligands enhance affinity at a designed metal-binding site. Chemistry & Biology. 1999 Sep;6(9):649–55. DOI: https://doi.org/10.1016/S1074-5521(99)80116-1.
• 40. Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies. 2004 Dec;1(4):337–41. DOI: https://doi.org/10.1016/j.ddtec.2004.11.007.
• 41. Kuti JL. OPTIMIZING ANTIMICROBIAL PHARMACODYNAMICS: A GUIDE FOR YOUR STEWARDSHIP PROGRAM. Revista Médica Clínica Las Condes. 2016 Sep;27(5):615–24. DOI: https://doi.org/10.1016/j.rmclc.2016.08.001.
• 42. Coraça-Huber DC, Dichtl S, Steixner S, Nogler M, Weiss G. Iron chelation destabilizes bacterial biofilms and potentiates the antimicrobial activity of antibiotics against coagulase-negative Staphylococci. Pathogens and Disease [Internet]. 2018 Jul 1 [cited 2021 May 3];76(5). Available from: https://academic.oup.com/femspd/article/doi/10.1093/femspd/fty052/5026171.