Published March 31, 2023 | Version v1

Investigation of antimicrobial potencies of mixed-ligand complexes of divalent metal ions with Barbituric acid and 2,2-Bipyridine

  • 1. Pure & Applied Chemistry Department, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
  • 2. Chemistry Department, Federal College of Education (Special), Oyo, Oyo State, Nigeria

Description

The development of resistance by many pathogenic microorganisms towards many conventional antibiotic drugs has now become one of the major worldwide health challenges, which requires a search for more effective drugs to combat the growing threat of widespread antibiotic resistance. Therefore, in an attempt to search for new and effective antibiotic drugs, antimicrobial potencies of mixed ligand complexes of Cu (II), Co (II), Ni (II) involving barbituric acid and 2,2-bipyridine chelating agents were examined. The mixed-ligand complexes were synthesized and the formation of the complexes was established using elemental analysis, metal analysis, melting points, solubility test, infra-red and Uv-visible analysis. The complexes were investigated for their pharmaceutical exploits against bacteria (Bacillus substilis and Staphylococcus aureus, Pseudomonas aeruginosa and Clostridium spp.) and four fungi (Aspergillus flavus, Aspergillus niger, Saccharomyces cerevisiae and Candida albican). Three conventional antibiotic drugs were employed as reference drugs. The formation of the metal complexes in ratio 1:1:1 and molecular formulas were confirmed via elemental and metal analyses. The purity of the metal complexes was ascertained by the sharp melting points. Infrared spectroscopic analysis revealed the formation of coordination bonds between the ligands and the metal ions through nitrogen and oxygen donors. The formation of the metal complexes was substantiated by UV-visible electronic transitions. The diversity of antimicrobial activities was displayed by the metal complexes against the pathogenic organisms at inhibitory zones of 6 mm – 25 mm. The metal complexes produced more significant antimicrobial activity than the standard drugs and succeeded where the standard drugs failed. The complexes could be considered potential antimicrobial agents to replace the less effective conventional antibiotic drugs. The toxicity of the metal complexes should be evaluated to establish their suitability for replacement.

Files

IRJSTEM_V3N2_2023_P03.pdf

Files (661.3 kB)

Name Size
md5:c1c814aa3b09f8c6807d2f80aabc49a4
661.3 kB Preview Download

Additional details

References

  • Akinyele, O.F, Fakola, E.G., Durosinmi, L.M., Ajayeoba, T.A., & Ayeni, A.O. (2020). Synthesis, characterization and antimicrobial activities of heteroleptic metal chelates of isoniazid and 2,2'-bipyridine. Bull. Chem. Soc. Ethiop., 34(3), 471-478.
  • Anacona, J.R. & Lopez, M. (2012). Mixed-ligand Nickel(II) complexes containing sulfathiazole and cephalosporin antibiotics: Synthesis, characterization, and antibacterial activity. International Journal of Inorganic Chemistry, 12, 1278-1284.
  • Andrejevi, T.P., Aleksic, I., Kljun, J., Pantovi´, B.V., Milivojevic, D., Vojnovic, S., Turel, I., Djuran, M.I., & Gliši, B.D. (2022). Zinc(II) complexes with dimethyl 2,20 -bipyridine-4,5- dicarboxylate: structure, antimicrobial activity and dna/bsa binding study. Inorganic, 10, 71. https://doi.org/ 10.3390/inorganics10060071
  • Arendrup, M.C. & Patterson, T.F. (2017). Multidrug-Resistant Candida: Epidemiology,molecular mechanisms, and treatment. The Journal of Infectious Diseases, 216(15), S445–S451.
  • Bruijnincx, P.C.A. & Sadler, P.J. (2008). New trends for metal complexes with anticancer activity. Current Opinion in Chemical Biology, 12(2), 197-206. https://doi.org/10.1016/j.cbpa.2007.11.013
  • Buwa, L.V. & Staden, J. (2005). Antibacterial and antifungal activity of traditional medicinal plants used against venereal diseases in South Africa. Journal of Ethnopharmacol, 103(1),139-142.
  • Canaparo, R., Foglietta, F., Giuntini, F., Della Pepa, C., Dosio, F., and Serpe, L. (2019). Recent developments in antibacterial therapy: focus on stimuli-responsive drug-delivery systems and therapeutic nanoparticles. Molecules 24(10), 1991. doi: 10.3390/molecules24101991
  • Coates, J. (2000). Interpretation of Infrared Spectra, A Practical approach. In Meyers R A (Ed.) Encyclopedia of analytical chemistry. John Wiley & Sons Ltd. pp. 15-37.
  • Cotton, F. A., Wilkinson, G., Murillo, C.A., & Bochmann, M. (1999). Advanced Inorganic Chemistry. John Wiley & Sons USA.
  • Czakis-Sulikowska, D., Czylkowska, A., Radwanska-Doczekalska, J., Grodzki, & Wojciechowska, E. (2007). Synthesis and characterization of new metal(II) complexes with formats and nitrogen donor ligands. Journal of Thermal Analysis and Caorimeter, 90, 557-564.
  • Das, A. (2009). Synthesis and characterization of mixed ligand complexes of cobalt(II) with some nitrogen and sulfur donors. Journal of Coordination Chemistry, 62, 2745-2754. https://doi.org/10.1080/00958970902870894.
  • Ekennia, A.C., Onwudiwe, D.C., Olasunkanmi, L.O., Osowole, A.A., & Ebenso, E.E. (2015). Synthesis, DFT calculation, and antimicrobial studies of novel zn(II), Co(II), Cu(II), and Mn(II) heteroleptic complexes containing benzoylacetone and dithiocarbamate. Bioinorganic Chemistry and Applications, 2015, 1-12 http://dx.doi.org/10.1155/2015/789063
  • Festus, C., Okafor, S.N., & Ekennia, A.C. (2019). Heteroleptic metal complexes of a pyrimidinyl based schiff base ligand incorporating 2,2′-bipyridine moiety: synthesis, characterization, and biological studies. Frontiers in Chemistry, 7, 862. doi: 10.3389/fchem.2019.00862
  • Fisher, M.C., Alastruey-Izquierdo, A., & Berman, J. (2022). Tackling the emerging threat of antifungal resistance to human health. Nature Reviews Microbiology, 1-15.
  • Francesca, S.L. (2011). Anti-microbial properties of scutellaria baicalensis and coptis chinensis, two traditional Chinese medicines. Bioscience Horizons, 1, 119-127.
  • Garcia, H., Toledo, M., Edwards, H., & De Oliveira, L. F. (2016). Vibrational and structural properties of barbiturate anions in supramolecular compounds. Vibrational Spectroscopy, 86, 102-109. https://doi.org/10.1016/j.vibspec.2016.07.002.
  • Gould D. (2013). Diagnosis, Prevention and treatment of fungal infections. Primary Health Care London. 22(6), 32-39.
  • Hamied Mihsen, H. & Kadham Shareef, N. (2018). Synthesis, characterization of mixed-ligand complexes containing 2,2-Bipyridine and 3-aminopropyltriethoxysilane. Journal of Physics Conference Series, 1032(1). doi:10.1088/1742-6596/1032/1/012066.
  • Hariprasath, K., Deepthi, B., Sudheer, I. Babu, P. Venkatesh, P., Sharfudeen, S., & Soumya, V. (2010). Metal complexes in drug research - a review. j. Chem. Pharm. Res, 2(4), 496-499.
  • Hasnain, S., Zulfequar, M., & Nishat, N. (2011). Metal containing polyurethanes from tetradentate schiff base ligand: their synthesis, characterization and biocidal activities. J. Coord. Chem. 64, 952–964.
  • Hassan, F.S.M., Kuran, W.S., Ibrahim, A.A., & Adam, F.A. (2020) Synthesis, Characterization and Biological Activity of Sodium Barbitone-GroupVIII Metals (viz. Ni(II), Pd(II) and Pt(II)) Complexes. Open Journal of Inorganic Nonmetallic Materials, 10, 1-14.
  • Ikotun, A.A, Ojo Y., Obafemi C.A., & Egharevba G.O. (2011). Synthesis and antibacterial activity of metal complexes of barbituric acid. African Journal of Pure and Applied Chemistry, 5(5), 97-103.
  • Ismail, E.H., Sabry, D.Y., Mahdy, H., & Khalil, M.M.H. (2014). Synthesis and characterization of some ternary metal complexes of curcumin with 1,10-phenanthroline and their anticancer applications. Journal of Scientific Research, 6(3), 509-519.
  • Jonathan, S.G. & Fasidi, I.O. (2003). Antimicrobial activities of two nigerian edible macro fungi-lycoperdon pusilum (bat. Ex) and lycoperdon giganteum (Pers.) African Journal of Biomedical Research, 6, 85-90.
  • Kani, I., Atlier, Q., & Guven, K. (2016). Mn(II) complexes with bipyridine, phenanthroline and benzoic acid: Biological and catalase-like activity. J. Chem. Sci., 128(4), 523–536.
  • Li, B. & Webster, T.J. (2018). Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopedic infections. J. Orthopaed. Res., 36, 22-32.
  • Mamdouh, S.M., Shaban, N.Z., & Ahmed, M.M. (2020). Structural chemistry and biological activity of some pyrimidine compounds and their transition metal complexes. International Journal of Scientific & Engineering Research, 11(6), 111-122.
  • Mathew, B., Suresh, J., & Vinod, D. (2012). Antitumor activity of 5-[(2E)-1- (1H-benzimidazol-2-yl) 3 substituted-phenylprop-2-en-1-ylidene] pyrimidine- 2,4,6(1H,3H,5H)-triones against Dalton's ascetic lymphoma in mice. Med Chem Res., 22, 3911-3917.
  • McCann, M., Kellett, A., Devereux, M., & Santos, A.L.S. (2012). Deciphering the antimicrobial 1193 activity of phenanthroline chelators. Curr. Med. Chem., 19, 2703-2714.
  • Osowole, A.A., Ekennia, A.C., & Osukwe, A.E. (2014). Synthesis, spectroscopic and antibacterial properties of some metal (ii) mixed-ligand complexes of riboflavin and 2,2'-bipyridine. research and reviews: Journal of Chemistry, 3(1), 32-37.
  • Palmucci, J., Mahmudov, K.T., Guedes da Silva, M.F.C., Marchetti, F., Pettinari, C., Petrelli, D., Vitali, L.A., Quassinti, L., Bramucci, M., Lupidi, G., & Pombeiro, A.J.L. (2016). DNA and BSA binding, anticancer and antimicrobial properties of Co(II), Co(II/III), Cu(II) and Ag(I) complexes of arylhydrazones of barbituric acid. RSC Adv., 6, 4237-4249.
  • Rhodes, J. (2019). Rapid worldwide emergence of pathogenic fungi. Cell Host & Microbe, 26(1), 12-14 https://doi.org/10.1016/j.chom.2019.06.009
  • Selvaganapathy, M. & Raman, N. (2016). Pharmacological activity of a few transition metal complexes: a short review. J. Chem. Biol. Therap. 1, 108. doi: 10.4172/2572-0406.1000108
  • Sigel, H., Operschall, B.P., Massoud, S.S., Song, B., & Griesser, R. (2006). Evidence for intramolecular aromatic-ring stacking in the physiological ph range of the monodeprotonated xanthine residue in mixed-ligand complexes containing xanthosinate 5'-monophosphate, Dalton Trans., 46, 5521-5529.
  • Teleb S.M., Askar M.E., El-Kalyoubi S.A., & Gaballa A.S. (2019). Synthesis, characterization and antimicrobial activities of some 5-Bromouracil Metal Ion Complexes. Bull. Chem. Soc. Ethiop., 33(2), 255-268.
  • Vivas, R., Andre´a, A., Barbosa, T., Dolabela, S.S., & Jain, S. (2019). Multidrug-resistant bacteria and alternative methods to control them: an overview. Microbial Drug Resistance, 25(6), 890-908.
  • Warra, A.A. (2011). Transition metal complexes and their application in drugs and cosmetics – A review. Journal of Chemical and Pharmaceutical Research, 3(4), 951–958.
  • World Health Organization (2021). Antimicrobial resistance. Retrieved from https://ahpsr.who.int/publications/i/item/global-action-plan-on-antimicrobial-resistance
  • Yang, X., Ye, W., Qi, Y., Ying, Y., & Xia, Z. (2021). Overcoming multidrug resistance in bacteria through antibiotics delivery in surface-engineered nano-cargos: recent developments for future nano-antibiotics. Frontiers in bioengineering and biotechnology, 9, 696514. doi: 10.3389/fbioe.2021.696514
  • Yilmaz, F., Yilmaz, V., Karakaya, H., & Büyükgüngör, O. (2014). 5,5-Diethylbarbiturate complexes of silver with 2,2′-bipyridine and 3-(2-pyridyl)propanol: Syntheses, crystal structures, spectroscopic, thermal and antimicrobial activity studies. Zeitschrift für Naturforschung B, 63(2), 134-138. doi:10.1515/znb-2008-0204.