Synthesis, Biological and Medicinal Evaluation of New Boric Acid Ester Derived From Antibiotic Drug with Some of Its Metal Complexes

Authors

  • Simaa Safaa Mahmoud Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.
  • Asmaa Mohammed Noori Department of Chemistry, College of Science, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.30526/37.1.3261

Keywords:

Metronidazole, Boric acid, spectroscopic techniques, Anticancer

Abstract

Synthesis of new ligand, namely [bis(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl) hydrogen borate] (BIB), utilizing the reaction of metronidazole with boric acid in mole ratio (2:1), as well as the metal complexes with [Ni(II) and Cu(II)], were synthesized. All synthesized compounds were characterized by utilizing spectroscopic techniques such as FTIR, 1H-NMR, thermal analysis (T.G., UV-Vis), and atomic absorption (A.A.S.), as well as micro elemental analysis (C.H.N.), melting point (m.p), magnetic susceptibility, molar conductivity, and chloride content measurements. All complexes were paramagnetic, and the electrolyte and the suggested geometries were tetrahedral for nickel and octahedral for copper. In addition, all the transition metal complexes produced were shown to be antibacterial and antifungal against the bacteria Staphylococcus aureus, Escherichia coli, and the fungus Candida. Also, metronidazole and the ligand were evaluated as anticancer agents against human breast cancer (MCF-7). The results showed that ligand was more active as an anticancer than metronidazole.

References

Çelik, A.; Ateş, A.N. The frequency of sister chromatid exchanges in cultured human peripheral blood lymphocyte treated with metronidazole in vitro. Drug and Chemical toxicology, 2006, 29(1),85-94. https://doi.org/10.1080/01480540500408663. DOI: https://doi.org/10.1080/01480540500408663

Kapoor, V.K.; Chadha, R.; Venisetty, P.K.; Prasanth, S. Medicinal significance of nitroimidazoles—some recent advances, Journal of Scientific& Industrial Research, 2003, 62,659-665. https://nopr.niscpr.res.in/bitstream/123456789/17609/1/JSIR%2062(7)%20659-665.pdf.

Ali, A.E.; Elasala, G.S.; Ibrahim, R.S. Synthesis, characterization, spectral, thermal analysis and biological activity studies of metronidazole complexes. Journal of Molecular Structure, 2019,1176,673-684. https://doi.org/10.1016/j.molstruc.2018.08.095.

Radko, L.; Stypuła-Trębas, S.; Posyniak, A.; Żyro, D.; Ochocki, J. Silver (I) complexes of the pharmaceutical agents metronidazole and 4-hydroxymethylpyridine: comparison of cytotoxic profile for potential clinical application. Molecules, 2019,24(10),1949. https://doi.org/10.3390/molecules24101949.

Siddappa, K.; Mallikarjun, M.; Reddy, P.T.; Tambe, M. Spectrophotometric determination of metronidazole through Schiff's base system using vanillin and PDAB reagents in pharmaceutical preparations. Eclética Química, 2008, 33,41-46. https://doi.org/ 10.1590/ S0100-46702008000400005. DOI: https://doi.org/10.1590/S0100-46702008000400005

Pal, R. Boric acid in organic synthesis: Scope and recent developments. ARKIVOC: Online Journal of Organic Chemistry. 2018. https://doi.org/10.24820/ark.5550190.p010.462. DOI: https://doi.org/10.24820/ark.5550190.p010.462

Gujral, S.S. UV-Visible spectral analysis of boric acid in different solvents: a case study. International Journal of Pharmaceutical Sciences and Research, 2015, 6(2),830. http://dx.doi.org/10.13040/IJPSR.0975-8232.6(2).830-34 DOI: https://doi.org/10.13040/IJPSR.0975-8232.6(2).830-34

Sulaiman, G.M.; Jabir, M.S.; Hameed, A.H. Nanoscale modification of chrysin for improved of therapeutic efficiency and cytotoxicity. Artificial cells, nanomedicine, and biotechnology, 2018, 46(sup1),708-720. https://doi.org/10.1080/21691401.2018.1434661. DOI: https://doi.org/10.1080/21691401.2018.1434661

Ogwuegbu Martin, O.C.; Kenechukwu, E.C.; Stanley, O.C.; Patricia, E.N.; Ebere, E.C. Stoichiometric determination of Fe (II), Ni (II) and Cu (II) complexes of metronidazole. International Journal of Chemical Science, 2019,3(1), 25-29. https://www.chemicaljournals.com/archives/2019/vol3/issue1/3-1-18.

Ramukutty, S.; Ramachandran, E. Crystal growth by solvent evaporation and characterization of metronidazole. Journal of crystal growth, 2012, 351(1),47-50. https://doi.org/10.1016/j.jcrysgro.2012.04.017. DOI: https://doi.org/10.1016/j.jcrysgro.2012.04.017

Al-Mathkhury, H.J.F.; Al-Dhamin, A.S.; Al-Taie, K.L. Antibacterial and antibiofilm activity of flaxseed oil. Iraqi Journal of Science, 2016,1086-1095. https://ijs.uobaghdad.edu.iq/index.php/eijs/article/view/7252.

Al-Azzawi, A.M.; Huseeni, M.D. Design and synthesis of novel homo and copolymerization based on 4-(N-maleimidylmethylbenzylidene)-4'-(N-citraconamic acid)-1, 1'-biphenyl. Egyptian Journal of Chemistry, 2022, 65(1),159-166. https://doi.org/10.21608/ejchem.2021.78334.3888.

Hasan, N.A.; Baqer, S.R. Preparation, characterization, theoretical and biological study of new complexes with mannich base, 2chloro–N-5-(Piperidin-1-ylmethylthio)-1, 3, 4-thiadiazol-2-yl) acetamide. Ibn AL-Haitham Journal For Pure and Applied Sciences, 2023, 36(1),260-271. https://orcid.org/0000-0003-3950-6183.

Obaleye, J.A.; Lawal, A. Synthesis, characterization and antifungal studies of some metronidazole complexes, JASEM , 2007,11(4),15-18. http://www.bioline.org.br/ja.

Gao, S.; Liu, Y.; Feng, S.; Lu, Z. Synthesis of borosiloxane/ polybenzoxazine hybrids as highly efficient and environmentally friendly flame retardant materials. Journal of Polymer Science Part A: Polymer Chemistry, 2017,55(14), 2390-2396. https://doi.org/10.1002/pola.28628. DOI: https://doi.org/10.1002/pola.28628

Jiang, N.; Zhou, Z.; Xu, W.; Ma, H.; Ren, F. Preparation of heat resistant boron-containing phenyl silicone oil and its initial degradation mechanism in air. Materials Research Express, 2021, 8(6),065304. http://dx.doi.org/10.1088/2053-1591/ac0178.

Waszczykowska, A.; Żyro, D.; Jurowski, P.; Ochocki, J. Effect of treatment with silver (I) complex of metronidazole on ocular rosacea: Design and formulation of new silver drug with potent antimicrobial activity. Journal of Trace Elements in Medicine and Biology, 2020, 61, 126531. https://doi.org/10.1016/j.jtemb.2020.126531.

Kalinowska-Lis, U.; Felczak, A.; Chęcińska, L.; Zawadzka, K.; Patyna, E.; Lisowska, K.; Ochocki, J. Synthesis, characterization and antimicrobial activity of water-soluble silver (I) complexes of metronidazole drug and selected counter-ions. Dalton Transactions, 2015, 44(17),8178-8189. https://doi.org/10.1039/C5DT00403A. DOI: https://doi.org/10.1039/C5DT00403A

Khaleel, A.M.N.; Jaafar, M.I. Synthesis and characterization of boron and 2-aminophenol Schiff base ligands with their Cu (II) and Pt (IV) complexes and evaluation as antimicrobial agents. Oriental Journal of Chemistry, 2017,33(5), 2394-2404. http://dx.doi.org/10.13005/ojc/330532 DOI: https://doi.org/10.13005/ojc/330532

Eugene-Osoikhia, T.T. Synthesis, characterisation and antimicrobial studies of metal (II) complexes of ofloxacin and metronidazole. Chem Search Journal, 2020,11(1),74-82. https://www.ajol.info/index.php/csj/article/view/197387.

Al-Jebouri, G.S.; Noorikhaleel, A.M. Synthesis of new boron compounds with amoxicillin and some of its metal complexes with use them in antibacterial, assessment of hepatoprotictive and kidney activity, anticancer and antioxidant applications. Synthesis, 2019,12(3). http://dx.doi.org/10.22159/ajpcr.2019.v12i3.30912.

Abdul-Ghani, A.J.; Khaleel, A. Synthesis and characterization of new schiff bases derived from N (1)-substituted isatin with dithiooxamide and their co (II), Ni (II), Cu (II), Pd (II), and Pt (IV) complexes. Bioinorganic Chemistry and Applications, 2009. https://doi.org/10.1155/2009/413175. DOI: https://doi.org/10.1155/2009/413175

Saja, A.J.; Asmma, M.N. Synthesis and characterization of new schiff base compound from levofloxacin and L-cysteine with its Cu(II) and Pt(IV) complexes and estimation antibacterial and antifungal activities, Biochemical and Cellular Archives, 2021, 21, 2187-2195. https://connectjournals.com/03896.2021.21.2187.

Khaleel, A.M.N. Synthesis and characterization of trihydro mono and dihydrobis (indole-3-acetic acid) borate ligands and some of their metal complexes. Iraqi Journal of Science, 2015, 56(4A),2762-2772. https://ijs.uobaghdad.edu.iq/index.php/eijs/article/view/9453.

Ali, I.; Wani, W.A.; Saleem, K. Empirical formulae to molecular structures of metal complexes by molar conductance. Synthesis and reactivity in inorganic, metal-organic, and nano-metal chemistry, 2013, 43(9),1162-1170. http://dx.doi.org/10.1080/15533174.2012.756898. DOI: https://doi.org/10.1080/15533174.2012.756898

Yoshino, T. Laboratory electrical conductivity measurement of mantle minerals. Surveys in Geophysics, 2010, 31(2),163-206. https://doi.org/10.1007/s10712-009-9084-0. DOI: https://doi.org/10.1007/s10712-009-9084-0

Hussein, N.A.; Abbas, A.K. Synthesis, spectroscopic characterization and thermal study of some transition metal complexes derived from caffeine azo ligand with some of their applications. Eurasian Chem Commun, 2022, 4(1),67-93. https://doi.org/10.22034/ecc.2022.307545.1245.

Czarnomysy, R.; Muszyńska, A.; Rzepka, Z.; Bielawski, K. Mechanism of anticancer action of novel imidazole platinum (II) complex conjugated with G2 PAMAM-OH dendrimer in breast cancer cells. International Journal of Molecular Sciences, 2021, 22(11), 5581. https://doi.org/10.3390/ijms22115581.

Al-Mathkhury, H.J.F.; Al-Dhamin, A.S.; Al-Taie, K.L. Antibacterial and antibiofilm activity of flaxseed oil. Iraqi Journal of Science, 2016,57(2B),1086-1095. https://ijs.uobaghdad.edu.iq/index.php/eijs/article/view/7252.

Abid, N.; Hamad, E.; Ibrahim, M.; Abid, H. Antibacterial and antibiofilm activities of taxifolin against vancomycin-resistant S. aureus (VRSA). Baghdad Journal of Biochemistry and Applied Biological Sciences, 2022, 3(04), 262-272. https://doi.org/10.47419/bjbabs.v3i04.126.

Ali, R.; Shanan, Z.J.; Saleh, G.M.; Abass, Q. Green synthesis and the study of some physical properties of MgO nanoparticles and their antibacterial activity. Iraqi Journal of Science, (2020),266-276. https://doi.org/10.21123/bsj.2023.8385. DOI: https://doi.org/10.24996/ijs.2020.61.2.9

Tawfeeq, H.K.; Hamid, M.; Al-Mathkhury, F.H.J. The prevalence of pseudomonas aeruginosa among Baghdad hospitalised patients. Medico-Legal Update, 2021, 21(2). https://doi.org/10.37506/mlu.v21i2.2749.

Sweedan, E.G. Estimate antimicrobial activity and anti-biofilm formation of bark cinnamomum zeylanicum on klebsiella pneumoniae isolated from urinary tract infections. Iraqi Journal of Science, 2018, 59(3C),1560-1566. https://ijs.uobaghdad.edu.iq/index.php/eijs/article/view/503.

Al-Ammash, M.S.J. Study the effect of alcoholic extract of Nigella sativa seeds on Trichomomas vaginalis in vitro. Ibn AL-Haitham Journal For Pure and Applied Science, 2017, 30(3),10-18. https://doi.org/10.30526/30.3.1596. DOI: https://doi.org/10.30526/30.3.1596

Downloads

Published

20-Jan-2024

Issue

Section

Chemistry

Publication Dates