Synthesis and Characterization of Fe(II) and Cu(II) Complexes of N-(benzothiazol-2-yl)benzamide Derivatives

Abstract

There is a need for chemicals that are resistant to these diseases because the sensitivity of microorganisms that cause diseases in living beings to the drugs used against them is gradually decreasing. Therefore, new Fe(II) {[Fe(abt)2(SO4)].H2O (1) and [Fe(smabt)2(SO4)].H2O (2)} and Cu(II) {[Cu(abt)2(Ac)2].4H2O (3) and [Cu(abt)2(Ac)2].4H2O (4)} complexes of N-(benzothiazol-2-yl)benzamide (abt) and 4-chloro-N-(6-sulfamoylbenzothiazol-2-yl)benzamide (smabt) were synthesized. The structures of 1-4 were suggested by elemental analysis, AAS, IR, molar conductivity and magnetic susceptibility methods. As a result of spectroscopic evaluation, compounds 1-4 were suggested to be nonionic and have tetrahedral geometry. Additionally, the antimicrobial activities of all substances against C. albicans (yeast), E. faecalis, E. coli, L. monocytogenes, S. aureus, P. aeruginosa and B. subtilis (bacteria) were investigated and compared with Ketoconazole, Fluconazole, Levofloxacin, Chloramphenicol, Vancomycin and Cefepime. All substances were observed to have antimicrobial properties against bacteria or yeast. When the antimicrobial activities of the starting materials (abt, smabt) and complexes (1-4) were compared, the same activity was observed against S. aureus (except 4), E. coli (except 1), B. subtilis, E. faecalis, L. monocytogenes bacteria, and C. albicans yeast. 4 showed less activity in S. aureus bacteria, 1 showed more activity in E. coli bacteria. In P. aeruginosa bacteria, the following effects were observed: 1 > 3, smabt > abt, 2, 4.

Keywords

• N-(benzothiazol-2-yl)benzamide
• 4-Chloro-N-(6-sulfamoylbenzothiazol-2-yl)benzamide
• Fe(II) complex
• Cu(II) complex
• Antimicrobial activity

N-(benzotiazol-2-il)benzamit türevlerinin Fe(II) ve Cu(II) Komplekslerinin Sentezi ve Karakterizasyonu

Öz

Canlılar üzerinde hastalıklara neden olan mikroorganizmaların karşı kullanılanilaçların duyarlılığı gitgide azalmasını nedeniyle bu hastalıklara karşı dirençbgösteren kimyasallara ihtiyaç bulunmaktadır. Bu nedenle, N-(benzotiazol-2-il)benzamit’in (abt) ve 4-kloro-N-(6-sülfamoilbenzotiazol-2-il)benzamit’in (smabt) yeni Fe(II) {[Fe(abt)2(SO4)].H2O (1) ve [Fe(smabt)2(SO4)].H2O (2)} ve Cu(II){[Cu(abt)2(Ac)2].4H2O (3) ve [Cu(smabt)2(Ac)2].4H2O (4)} kompleksleri sentezlendi. 1-4’ün yapıları, element analiz, AAS, IR, molar iletkenlik ve manyetik duyarlılık yöntemleri ile önerildi. Spektroskopik değerlendirmenin bir sonucu olarak, 1-4 bileşiklerinin iyonik olmayan ve tetrahedral geometriye sahip olduğu önerildi. Ayrıca, tüm maddelerin C. albicans (maya), E. faecalis, E. coli, L.monocytogenes, S. aureus, P. aeruginosa ve B. subtilis (bakteri) karşı antimikrobiyal aktiviteler incelendi ve Ketokonazol, Flukonazol, Levofloksasin, Kloramfenikol, Vankomisin ve Sefepim ile karşılaştırıldı. Tüm maddelerin bakterilere veya mayaya karşı antimikrobiyal özellik gösterdiği gözlendi. Başlangıç maddeleri (abt, smabt) ile komplekslerin (1-4) antimikrobiyal aktiviteleri karşılaştırıldığında, S. aureus (4 hariç), E. coli (1 hariç), B. subtilis, E. faecalis, L. monocytogenes bakterileri ve C. albicans mayasında aynı aktivite gözlenmiştir. S. aureus bakterisinde 4 daha az, E. coli bakterisinde 1 daha çok etki göstermiştir. P. aeruginosa bakterisinde ise 1 > 3, smabt > abt, 2, 4 şeklinde etki gözlenmiştir.

Anahtar Kelimeler

• N-(benzotiazol-2-il)benzamit
• 4-Kloro-N-(6-sülfamoilbenzotiazol-2-il)benzamit
• Fe(III) kompleksi
• Cu(II) kompleksi
• Antimikrobiyal aktivite

References

1. [1] R. Ali, N. Siddiqui, “Biological Aspects of Emerging Benzothiazoles: A Short Review”. Academic Edi-tor: Gabriel Navarrete-Vazquez, Kaustubha Mohanty, Indian Institute of Technology Guwahati, India, 2013.
2. [2] P.S. Yadav, G.P. Senthilkumar, “Benzothiazole: different methods of synthesis and diverse biological ac-tivities”. Int. J. Pharm. Sci. Drug. Res., vol. 3, no. 1–7, 2011.
3. [3] G. Achaiah, N. S. Goud, K.P. Kumar, P. Mayuri, “Review on 2-substituted benzothiazoles: diversity of synthetic methods and biological activities”. Int. J. Pharm. Sci. Drug. Res., vol. 7, no. 4, pp. 1375-1382, 2016.
4. [4] R. Yadav, D. Meena, K. Singh, R. Tyagi, Y. Yadav, R. Sagar, “Recent advances in the synthesis of new benzothiazole based anti-tubercular compounds”. RSC Adv., vol. 13, pp. 21890-21925, 2023.
5. [5] M. Singh, H. Verma, P. Bhandu, M. Kumar, G. Narendra, S. Choudhary, P.K. Singh, O. Silakari, “Network analysis guided designing of multi-targeted anti-fungal agents: synthesis and biological evalua-tion”. J. Mol. Struct., vol. 1272, 134128, 2023.
6. [6] X. Wang, M. Zhao, Y. Chang, S. Guan, M. Li, H. Yang, M. Sun, “Identification of novel benzothiazole derivatives as inhibitors of NEDDylation pathway to inhibit the progression of gastric cancer”. Bioorg. Med. Chem. Let., vol. 100, pp. 129647, 2024.
7. [7] N. Sharma, N. Srivastava, A. Kaushal, B. Das, A. Vashistha, L. Kumar, R. Kumar, A.K. Yadav, “Synthe-sis, in silico study and biological evaluation of N-(benzothiazol/thiazol-2-yl)benzamide derivatives as qu-orum sensing inhibitors against pseudomonas aeruginosa”. Chem. Biodiv., vol. 20, no. 9, pp. e202300647, 2023.
8. [8] L. Shadap, N. Agarwal, V. Chetry, K.M. Poluri, W. Kaminsky, M.R. Kollipara, “Arene ruthenium, rho-dium and iridium complexes containing benzamide derivative ligands: Study of interesting bonding mo-des, antibacterial, antioxidant and DNA binding studies”. J. Organomet. Chem., vol. 937, pp. 121731, 2021.

9. [9] E.S. Al-Farraj, A. Fetoh, “Synthesis of new Fe(III), Co(II), and Cr(III) complexes of N-(benzo[d]thiazol-2-ylcarbamothioyl)benzamide (H2L2): Structural characterization and biological activities”. App. Orga-nomet. Chem., vol. 37, no. 11, pp. e7248, 2023.
10. [10] S. Bonnett, J. Jee, S. Chettiar, Y. Ovechkina, A. Korkegian, E. Greve, J. Odingo, T. Parish, “Identifica-tion of 2-amino benzothiazoles with bactericidal activity against Mycobacterium tuberculosis”. Microbio. Spect., vol. 11, no. 1, pp. 1-17, 2023.
11. [11] S.R. Gurram, M.A. Azam, “Design, synthesis and biological evaluation of some novel N'-(1,3-benzothiazol-2-yl)-arylamide derivatives as antibacterial agents”. Chem. Papers, vol. 75, no. 10, pp. 5435-5452, 2021.
12. [12] M. B. Taj, S.A. Tirmizi, A. Raheel, W. Alelwani, D. Hajjar, A.A. Makki, U. Ali, M. Darroudi, H.B.M. Ali, “Facile synthesis of N-phenyl benzamidine derivatives, their skin protecting, and anti-aging activity”. Russian J. Gen. Chem., vol. 88, no. 11, pp. 2425-2431, 2018.
13. [13] I. Sovic, M. Cindric, N. Perin, I. Bocek, I. Novakovic, A. Damjanovic, T. Stanojkovic, M. Zlatovic, M. Hranjec, B. Bertosa, “Biological potential of novel methoxy and hydroxy substituted heteroaromatic ami-des designed as promising antioxidative agents: synthesis, 3D-QSAR analysis, and biological activity”. Chem. Res. Toxic., vol. 32, no. 9, pp. 1880-1892, 2019.
14. [14] Y. Wei, M. Zhang, Z. Lyu, G. Yang, T. Tian, M. Ding, X. Zeng, F. Xu, P. Wang, F. Li, Y. Liu, Z. Cao, J. Lu, X. Hong, H. Wang “Benzothiazole amides as TRPC3/6 inhibitors for gastric cancer treatment”. ACS Omega, vol. 6, no. 13, pp. 9196-9203, 2021, doi: 10.1021/acsomega.1c00514.
15. [15] F. Ricci, A. Angeli, F. Mancuso, L. De Luca, C.T. Supuran, R. Gitto, “Screening campaign and docking ınvestigations in ıdentifying new hit compounds as inhibitors of human carbonic anhydrases expressed in tumour cells”. ChemMedChem, vol. 18, no. 20, pp. e202300330, 2023.
16. [16] J.T. Chiou, Y.Y. Wu, Y.C. Lee, L.S. Chang, “BCL2L1 inhibitor A-1331852 inhibits MCL1 transcription and triggers apoptosis in acute myeloid leukemia cells”. Biochem. Pharm., vol. 215, pp. 115738, 2023.
17. [17] R.F.C. Dias, B.M.R.M. Ribeiro, N.M. Cassani, D.N. Farago, G.A. Antoniucci, R.E. de Oliveira Rocha, F. de Oliveira Souza, E.J. Pilau, A.C.G. Jardim, R.S. Ferreira, C.O.R. Júnior, “Discovery and structural op-timization of a new series of N-acyl-2-aminobenzothiazole as inhibitors of Zika virus”. Bioorg. Med. Chem., vol. 95, no. 15, pp. 117488, 2023.
18. [18] M. Dittmar, K. Whig, J. Miller, B. Kamalia, S. Suppiah, L. Perelygina, K.E. Sullivan, D.C. Schultz, S. Cherry, “Nucleoside analogs NM107 and AT-527 are antiviral against rubella virus”. PNAS Nexus, vol. 2, no. 9, pp. 1-8, 2023.
19. [19] H. Maus, F. Barthels, S.J. Hammerschmidt, K. Kopp, B. Millies, A. Gellert, A. Ruggieri, T. Schirmeister, “SAR of novel benzothiazoles targeting an allosteric pocket of DENV and ZIKV NS2B/NS3 proteases”. Bioorg. Med. Chem., vol. 47, pp. 116392, 2021.
20. [20] E.S. Leal, M.G. Aucar, L.G. Gebhard, N.G. Iglesias, M.J. Pascual, J.J. Casal, A.V. Gamarnik, C.N. Cava-sotto, M. Bollini, “Discovery of novel dengue virus entry inhibitors via a structure-based approach”. Bioorg. Med. Chem., vol. 27, no. 16, pp. 3851-3855, 2017.
21. [21] M. Jyothi, V.L. Ranganatha, H.A. Khamees, M.J.N. Khadri, S.A. Khanum, “Design, synthesis, characte-rization and analysis of anti-inflammatory properties of novel N-(benzo[d]thiazol-2-yl)-2-[phenyl(2-(piperidin-1-yl)ethylamino]benzamides and N-(benzo[d]thiazol-2-yl)-2-[phenyl (2-morpholino)ethylamino]benzamides derivatives through in vitro and in silico approach”. J. Iranian Chem. Soc., vol. 20, no. 4, pp. 861-873, 2023.
22. [22] D. Muhammed Aziz, S. A. Hassan, A.A.M. Amin, M. N. Abdullah, K. Qurbani, S. B. Aziz, “A synergis-tic investigation of azo-thiazole derivatives incorporating thiazole moieties: a comprehensive exploration of their synthesis, characterization, computational insights, solvatochromism and multimodal biological activity assessment”. RSC Adv., vol. 13, no. 49, pp. 34534-34555, 2023.
23. [23] M.B. Taj, A. Raheel, W. Alelwani, N. Babteen, S. Kattan, A. Alnajeebi, M. Sharif, R.H. Ahmad, Abbas, A. Hazeeq, S.A. Tirmizi, H.B.M. Ali, “One-Pot CuO-catalyzed green synthesis of N(N')-arylbenzamidines as potential enzyme inhibitors”. Russian J. Org. Chem., vol. 55, no. 7, pp. 1047-1052, 2019.
24. [24] T.J.W.J.D. Lapierre, D.N. Farago, M.G.F. de Moura Lodi Cruz, D. de Melo Resende, A.C.R. de Oliveira, B.R. M. dos Santos, F. de Oliveira Souza, S. Michelan-Duarte, R.C. Chelucci, A.D. Andricopulo, L.L.G. Ferreira, E.J. Pilau, S.M.F. Murta, C.O.R. Júnior, “Evaluation and discovery of novel benzothiazole deri-vatives as promising hits against Leishmania İnfantum”. Chem. Bio. Drug Des., vol. 103, no. 4, pp. e14525, 2024.
25. [25] S. Ramos, A. Vicente-Blazquez, M. Lopez-Rubio, L. Gallego-Yerga, R. Alvarez, R. Pelaez, “Frentizole, a nontoxic ımmunosuppressive drug, and İts analogs display antitumor activity via tubulin inhibition”. In-ter. J. Mol. Sci., vol. 24, no. 24, pp. 17474, 2023.
26. [26] M.G. Chini, A. Giordano, M. Potenza, S. Terracciano, K. Fisher, M.C. Vaccaro, E. Colarusso, I. Bruno, R. Riccio, A. Koeberle, O. Werz, G. Bifulco, “Targeting mPGES-1 by a combinatorial approach: ıdentifi-cation of the aminobenzothiazole scaffold to suppress PGE levels”. ACS Med. Chem. Let., vol. 11, no. 5, pp. 783-789, 2020.
27. [27] M.M.F. Ismail, H.G. Abdulwahab, E.S. Nossier, N.G. El Menofy, B.A. Abdelkhalek, “Synthesis of novel 2-aminobenzothiazole derivatives as potential antimicrobial agents with dual DNA gyrase/topoisomerase IV inhibition”. Bioorg. Chem., vol. 94, pp. 103437, 2020.
28. [28] A.A. Irzoqi, F. A. Salman, Y. K. Alasadi, M. A. Alheety, “Synthesis and structural characterization of palladium(II) mixed-ligand complexes of N-(benzothiazol-2-yl)benzamide and 1,2-bis(diphenylphosphino)ethane”. Inorg. Chem., vol. 60, no. 24, pp. 18854-18858, 2021.
29. [29] J. Angulo-Cornejo, M. Lino-Pacheco, R. Richter, L. Hennig, K.H. Hallmeier, L. Beyer, “Metal chelates of N-benzothiazol-2-yl-, N-benzoxazol-2-yl- and N-(1H-benzimidazol-2-yl)-benzamide”. Inorg. Chim. Acta, vol. 305, no. 1, pp. 38–45, 2000.
30. [30] H. Zheng, Y.X. Li, W.C. Xiong, X.C. Wang, S.S. Gong, S. Pu, R. Shi, Q. Sun, “Mechanistic insights into diversified photoluminescence behaviors of BF2 complexes of N-benzoyl 2-aminobenzothiazoles”. Phys. Chem. Chem. Phy., vol. 26, no. 15, pp. 11611-11617, 2024.
31. [31] U. Caruso, B. Panunzi, A. Roviello, M. Tingoli, A. Tuzi, “Two aminobenzothiazole derivatives for Pd(II) and Zn(II) coordination”. Inorg. Chem. Commun., vol. 14, no. 1, pp. 46-48, 2011, doi: 10.1016/j.inoche.2010.09.027.
32. [32] H. İlkimen, “N-(6-sülfamoilbenzotiyazol-2-il)’in Amit Türevlerinin Metal Komplekslerinin İncelenmesi”. 4th International Conference on Engineering, Natural and Social Sciences ICENSOS 2024, 22-23 October 2024, Konya, Türkiye.
33. [33] K. Nakamoto, “Infrared and raman spectra of inorganic and coordination compounds” 5th ed NewYork: Wiley-Interscience, pp 232, 1997.
34. [34] W.J. Geary, “The use of conductivity measurements in organic solvents for the characterisation of coor-dination compounds,” Coord. Chem. Rev., vol. 7, no. 1, pp. 81-122, 1971.
35. [35] C. Spampinato, D. Leonardi, “Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents”. Biomed. Res. Int., vol. 2013, no. 1, pp. 204237, 2013.
36. [36] B.G. Tweedy, “Synthesis and assessment of antibacterial activities of ruthenium(III) mixed ligand comp-lexes containing 1,10-phenanthroline and guanide”. Phytopath., vol. 55, pp. 910-914, 1964.
37. [37] Z.H. Chohan, M. Arif, M.A. Akhtar, C. Supuran, “Metal-based antibacterial and antifungal agents: synt-hesis, characterization, and in vitro biological evaluation of Co(II), Cu(II), Ni(II), and Zn(II) complexes with amino acid-derived compounds”. Bioinorg. Chem. Appl., vol. 2006, pp. 83131, 2006.
38. [38] N. Raman, S.J. Raja, A. Sakthivel, “Transition metal complexes with Schiff-base ligands: 4-aminoantipyrine based derivatives–a review”. J. Coord. Chem., vol. 62, no. 5, pp. 691-709, 2009.