Determination of Cytotoxicity of Zinc 2-Bromobenzoate with Nicotinamide and N,N'-Diethylnicotinamide Complexes

Abstract

Benzoic acid and its derivatives and their metal complexes, which have antimicrobial, anticancer, antituberculosis and antioxidant properties, are biologically active molecules. Although there are many studies on the biological activity of these compounds, studies on the determination of their toxicity are limited. In the presented study, the cytotoxic properties of the previously synthesized diaquabis(2-bromobenzoato-κO)bis(nicotinamide-κN1)zinc(II) (ZnBrBANA) and diaquabis(2-bromobenzoato-κO)bis(N,N'-diethylnicotinamide-κN1)zinc(II) (ZnBrBADENA) complexes were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a colorimetric method, was used to determine the cytotoxicity of complexes on human peripheral lymphocyte cells. Besides, cytotoxicity of dimethylsulfoxide (DMSO) which is crystal solvent and 2-bromobenzoic acid (BrBA), nicotinamide (NA), and N,N'-dietyhlnicotinamide (DENA) which are starting compounds of the complexes was also evaluated. According to the results of MTT method, It has been determined that both complexes and starting components except BrBA cause cytotoxicity on lymphocyte cells at the concentration range of 62.5-500 ppm. In addition, it was determined that the BrBA and DMSO at the same concentration range do not show any cytotoxic effect on lymphocyte cells. It was observed that the synthesized complexes were more toxic at each concentration than the starting components. Therefore, the toxic effects of the complexes used as drug active ingredients should be followed up with new studies.

Keywords

• Cytotoxicity
• MTT assay
• 2-Bromobenzoic acid
• Zinc Complex

References

1. Bakhtiar R., Ochiai E.I. (1999). Pharmacological applications of inorganic complexes. General Pharmacology: The Vascular System, 32(5), 525–540. https://doi.org/10.1016/S0306-3623(98)00223-7
2. Balan G., Burduniuc O., Usataia I., Graur V., Chumakov Y., Petrenko P., Gudumac V., Gulea A., Pahontu E. (2020). Novel 2‐formylpyridine 4‐allyl‐ S ‐methylisothiosemicarbazone and Zn(II), Cu(II), Ni(II) and Co(III) complexes: Synthesis, characterization, crystal structure, antioxidant, antimicrobial and antiproliferative activity. Applied Organometallic Chemistry, 34(3). https://doi.org/10.1002/aoc.5423
3. Bhattacharyya M. K., Gogoi A., Chetry S., Dutta D., Verma A. K., Sarma B., Franconetti A., Frontera A. (2019). Antiproliferative evaluation and supramolecular association in Mn(II) and Zn(II) bipyridine complexes: Combined experimental and theoretical studies. Journal of Inorganic Biochemistry, 200, 110803. https://doi.org/10.1016/j.jinorgbio.2019.110803
4. Cavicchi G. S. (1959). Micro-chemical differentiation of several N, N-diethylamides in pharmaceutical use. Il Farmaco; Edizione Pratica, 14(4), 241–250.
5. Heine J., Müller-Buschbaum K. (2013). Engineering metal-based luminescence in coordination polymers and metal–organic frameworks. Chemical Society Reviews, 42(24), 9232. https://doi.org/10.1039/c3cs60232j
6. Hökelek T., Dal H., Tercan B., Özbek F. E., Necefoğlu H. (2009a). Diaquabis(2-bromobenzoato-κO)bis(nicotinamide-κN 1)zinc(II). Acta Crystallographica Section E Structure Reports Online, 65(5), m607–m608. https://doi.org/10.1107/S1600536809015645
7. Hökelek T., Dal H., Tercan B., Özbek F. E., Necefoğlu H. (2009b). Diaquabis(2-bromobenzoato-κO)bis(N,N-diethylnicotinamide-κN1)zinc(II). Acta Crystallographica Section E Structure Reports Online, 65(5), m481–m482. https://doi.org/10.1107/S160053680901191X
8. Hökelek T., Yılmaz F., Tercan B., Sertçelik M., Necefoğlu H. (2009). catena -Poly[[(4-formylbenzoato-κ O 1 )(isonicotinamide-κ N 1 )zinc(II)]-μ-4-formylbenzoato-κ 2 O 1 : O 1′ ]. Acta Crystallographica Section E Structure Reports Online, 65(11), m1399–m1400. https://doi.org/10.1107/S160053680904241X

9. Jamalian A., Miri R., Firuzi O., Amini M., Moosavi-Movahedi A. A., Shafieea A. (2011). Synthesis, cytotoxicity and calcium antagonist activity of novel imidazolyl derivatives of 1,8-acridinediones. Journal of the Iranian Chemical Society, 8(4), 983–991. https://doi.org/10.1007/BF03246554
10. Jozef H., Danica Č., Lawson M. K., Růžičková Z., Jorík V., Koman M., Valko M., Kozlevčar B., Moncol J. (2016). Self-assembly hydrogen-bonded supramolecular arrays from copper(II) halogenobenzoates with nicotinamide: Structure and EPR spectra‡. Chemical Papers, 70(1). https://doi.org/10.1515/chempap-2015-0203
11. Krajníková A., Győryová K., Hudecová D., Kovářová J., Vargová Z. (2011). Thermal decomposition and antimicrobial activity of zinc(II) 2-bromobenzoates with organic ligands. Journal of Thermal Analysis and Calorimetry, 105(2), 451–460. https://doi.org/10.1007/s10973-010-1161-6
12. Krishna R. (2015). Methodologies for evaluation of metal–organic frameworks in separation applications. RSC Advances, 5(64), 52269–52295. https://doi.org/10.1039/C5RA07830J
13. Li L., Yang J., Li J., Chen Y., Li J. (2013). Adsorption and molecular simulation of CO2 and CH4 in two-dimensional metal–organic frameworks with the same layered substrate. CrystEngComm, 15(34), 6782-6789. https://doi.org/10.1039/c3ce40838h
14. Liguori P. F., Valentini A., Palma M., Bellusci A., Bernardini S., Ghedini M., Panno M. L., Pettinari C., Marchetti F., Crispini A., Pucci D. (2010). Non-classical anticancer agents: synthesis and biological evaluation of zinc(II) heteroleptic complexes. Dalton Transactions, 39(17), 4205. https://doi.org/10.1039/b922101h
15. Lu Y., Xu W., Hu K., Jin S., Sun L., Liu B., Wang D. (2019). Synthesis and structural characterizations of nine non-covalent-bonded Zn2+, and Cd2+ supramolecules based on 3,5-dimethylpyrazole and carboxylates. Polyhedron, 159, 408–425. https://doi.org/10.1016/j.poly.2018.11.029
16. Mjos K. D., Orvig, C. (2014). Metallodrugs in Medicinal Inorganic Chemistry. Chemical Reviews, 114(8), 4540–4563. https://doi.org/10.1021/cr400460s
17. Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65(1), 55–63. https://doi.org/10.1016/0022-1759(83)90303-4
18. Nashre-ul-Islam S. M, Dutta D., Verma A. K., Nath H., Frontera A., Sharma P., Bhattacharyya M. K. (2019). Antiproliferative evaluation and supramolecular association involving electrostatically enhanced π-π interaction in isostructural coordination solids of Mn(II), Co(II) and Zn(II) chlorobenzoates: Experimental and theoretical studies. Inorganica Chimica Acta, 498, 119161. https://doi.org/10.1016/j.ica.2019.119161
19. Özbek F. E., Sertçelik M., Yüksek M., Uğurlu G., Tonbul A. M., Necefoğlu H., Hökelek T. (2019). Synthesis and Crystallographic, Absorption and Emission Studies of 4-Pyridine Carboxamide of Zn(II) 4-Chlorophenylacetate. Journal of Fluorescence, 29(5), 1265–1275. https://doi.org/10.1007/s10895-019-02440-x
20. Ozturk C., Akbaba G. B. (2019). Investigation of Antibacterial and Cytotoxic Properties of Mix Ligand Complex of Zinc 2-Fluorobenzoate with Nicotinamide. Hittite Journal of Science & Engineering, 6(4), 269–274. https://doi.org/10.17350/HJSE19030000157
21. Pucci D., Crispini A., Mendiguchía B.S., Pirillo S., Ghedini M., Morelli S., De Bartolo L. (2013). Improving the bioactivity of Zn(ii)-curcumin based complexes. Dalton Transactions, 42(26), 9679-9687. https://doi.org/10.1039/c3dt50513h
22. Rimoldi M., Howarth A. J., DeStefano M. R., Lin L., Goswami S., Li P., Hupp J.T., Farha O.K. (2017). Catalytic Zirconium/Hafnium-Based Metal–Organic Frameworks. ACS Catalysis, 7(2), 997–1014. https://doi.org/10.1021/acscatal.6b02923
23. Sertçelik M., Çaylak Delibaş N., Necefoğlu H., Hökelek T. (2012). Diaquabis(N,N-diethylnicotinamide-κN1)bis(4-formylbenzoato-κO1)zinc. Acta Crystallographica Section E Structure Reports Online, 68(8), m1067–m1068. https://doi.org/10.1107/S1600536812031200
24. Sertçelik M., Özbek F. E., Sugeçti̇ S., Necefoğlu H. (2018). Synthesis Of Izonicotınamide Complexes Of 4-Formilbenzoate with Co (II), Cu (II) And Zn (II); Investigation of Spectroscopic, Thermal Properties and Antibacterial Activıties. Journal of the Institute of Science and Technology, 8(4), 189–195. https://doi.org/10.21597/jist.408109
25. Taşdemir E., Özbek F. E., Sertçelik M., Hökelek T., Çelik R. Ç., Necefoğlu H. (2016). Supramolecular complexes of Co(II), Ni(II) and Zn(II) p-hydroxybenzoates with caffeine: Synthesis, spectral characterization and crystal structure. Journal of Molecular Structure, 1119, 472–478. https://doi.org/10.1016/j.molstruc.2016.05.006
26. Teixeira R., Barbosa L., Maltha C., Rocha M., Bezerra D., Costa-Lotuf L., Pessoa C., Moraes M.O. (2007). Synthesis and Cytotoxic Activity of Some 3-Benzyl-5-Arylidenefuran-2(5H)-ones. Molecules, 12(5), 1101–1116. https://doi.org/10.3390/12051101
27. Wang D., Liu X., Ye X., Yuan K., Xing X., Xie Y., Chen Z., Li B., Huang C., Kuang T., Cui L., Yu Z., Wu D. (2020). Synthesis of low toxicity metal-organic framework carrier for drug release. Materials Express, 10(6), 934–941. https://doi.org/10.1166/mex.2020.1707
28. Zhu Z., Xu C., Wang M., Zhang X., Wang H., Luo Q., Bi S., Fan Y. (2017). Six Co(II) Coordination Polymers Based on Two Isomeric Semirigid Ether-Linked Aromatic Tetracarboxylate Acid: Syntheses, Structural Comparison, and Magnetic Properties. Crystal Growth & Design, 17(10), 5533–5543. https://doi.org/10.1021/acs.cgd.7b01070