Sains Malaysiana 49(8)(2020): 1891-1904

http://dx.doi.org/10.17576/jsm-2020-4908-11

Isatin Endowed Metal Chelates as Antibacterial and Antifungal Agents

(Isatin Pembawa Logam Pengkelat sebagai Agen Anti-Bakteria dan Anti-Kulat)

SEHER KHALID¹, SAJJAD HUSSAIN SUMRRA*² & ZAHID HUSSAIN CHOHAN³

¹Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan

²Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan

³Department of Chemistry, University College of Management & Sciences, Khanewal 58150, Pakistan

Received: 17 November 2019/Accepted: 3 April 2020

ABSTRACT

A new series of 5-chloroindoline-2,3-dione (isatin) derived ligands (L¹)-(L⁴) were prepared by reacting isatin with various diamines such as ethane-1,2-diamine, propane-1,3-diamine, butane-1,4-diamine, and benzene-1,2-diamine in an equimolar ratio to give 3-[(2-aminoethyl)imino]-5-chloro-1,3-dihydro-2H-indol-2-one (L¹), 3-[(3-aminopropyl)imino]-5-chloro-1,3-dihydro-2H-indol-2-one (L²), 3-[(4-aminobutyl)imino]-5-chloro-1,3-dihydro-2H-indol-2-one (L³) and 3-[(2-aminophenyl)imino]-5-chloro-1,3-dihydro-2H-indol-2-one (L⁴). All ligands acted as tridentate possessing three active sites, isatin-O, azomethine-N, and amino-N for binding with the metal atoms. The structures of the isatin based Schiff bases were elucidated through their spectral (infrared, ultraviolet, nuclear magnetic resonance, and mass spectra), physical (melting point and solubility) and analytical (C, N, H %) data. The prepared ligands were reacted with Co(II), Ni(II), Cu(II), and Zn(II) transition metals in 1:2 molar ratio (metal:ligand) to form their complexes. IR, UV, NMR, conductance, magnetic moment, and elemental analysis was used to characterize the metal complexes. Metals based isatins were evaluated for their in-vitro antimicrobial properties against selected fungal and bacterial species. The anti-bacterial and anti-fungal results showed the metal chelates to be more biologically active than their parent uncomplexed ligands.

Keywords: Antibacterial and antifungal activity; isatin transition metal(II) complexes

ABSTRAK

Siri baru 5-kloroindolin-2,3-dione (isatin) ligan terbitan (L¹)-(L⁴) dihasilkan melalui tindak balas isatin dengan pelbagai diamina seperti etana-1,2-diamin, propana-1,3-diamin, butana-1,4-diamin dan benzena-1,2-diamin dalam nisbah ekuimolar untuk membentuk 3-[(2-aminoetil) imino]-5-kloro-1,3-dihidro-2H-indol-2-one (L¹), 3-[(3-aminopropil) imino]-5-kloro-1,3-dihidro-2H-indol-2-one (L²), 3-[(4-aminobutil) imino]-5-kloro-1,3-dihydro-2H-indol-2-one (L³) dan 3-[(2-aminofenil)imino]-5-kloro-1,3-dihidro-2H-indol-2-one (L⁴). Semua ligan bertindak sebagai tridentat yang mempunyai tiga tapak aktif, isatin-O, azometine-N dan amino-N dengan mengikat atom logam. Struktur isatin berasaskan bes Schiff dijelaskan melalui spektrumnya (inframerah, ultraungu, resonansi magnetik nuklear dan spektra jisim), fizikal (takat lebur dan kelarutan) dan data analisis (C, N, H%). Ligan tersebut juga bertindak balas dengan logam peralihan Co(II), Ni(II), Cu(II) dan Zn(II) dalam nisbah molar 1: 2 (logam: ligan) untuk membentuk kompleks mereka. IR, UV, NMR, konduktans, momen magnetik dan analisis unsur digunakan untuk mencirikan kompleks logam. Isatin berasaskan logam dinilaikan untuk sifat antimikrobnya secara in vitro terhadap beberapa spesies kulat dan bakteria terpilih. Hasil kajian anti-bakteria dan anti-kulat ini menunjukkan bahawa pengkelat logam adalah lebih aktif secara biologinya berbanding ligan induk yang bukan kompleks.

Kata kunci: Aktiviti antibakteria dan antikulat; kompleks logam(II) peralihan isatin

REFERENCES

Abdul-Ghani, A.J. & Khaleel, A.M.N. 2009. 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: 1-12.

Aboul-Fadl, T. & Bin-Jubair, F.A 2010. Anti-tubercular activity of isatin derivatives. International Journal of Research in Pharmaceutical Sciences 1(2): 113-126.

Amjad, M., Sumrra, S.H., Akram, M.S. & Chohan, Z.H. 2016. Metal-based ethanolamine-derived compounds: A note on their synthesis, characterization and bioactivity. Journal of Enzyme Inhibition and Medicinal Chemistry 31(4): 88-97.

Arjunan, V., Saravanan, I., Ravindran, P. & Mohan, S. 2009. Structural, vibrational and DFT studies on 2-chloro-1H-isoindole-1,3(2H)-dione and 2-methyl-1H-isoindole-1,3(2H)-dione. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 74(3): 642-649.

Bagihalli, G.B., Badami, P.S. & Patil, S.A. 2009. Synthesis, spectral characterization and in vitro biological studies of Co(II), Ni(II) and Cu(II) complexes with 1,2,4-triazole Schiff bases. Journal of Enzyme Inhibition and Medicinal Chemistry 24(2): 381-394.

Balhausen, C.J. 1962. An Introduction to Ligand Field Theory. New York: McGraw-Hill.

Beauchard, A., Ferandin, Y., Frère, S., Lozach, O., Blairvacq, M., Meijer, L., Thiery, V. & Besson, T. 2006. Synthesis of novel 5-substituted indirubins as protein kinases inhibitors. Bioorganic & Medicinal Chemistry 14(18): 6434-6443.

Bekircan, O. & Bektas, H. 2008. Synthesis of Schiff and Mannich bases of isatin derivatives with 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones. Molecules 13(9): 2126-2135.

Chohan, Z.H., Supuran, C.T., Hadda, T.B., Nasim, F.H. & Khan, K.M. 2009. Metal based isatin-derived sulfonamides: Their synthesis, characterization, coordination behavior and biological activity. Journal of Enzyme Inhibition and Medicinal Chemistry 24(3): 859-870.

Chohan, Z.H., Shaikh, A.U. & Supuran, C.T. 2006. In-vitro antibacterial, antifungal and cytotoxic activity of cobalt(II), copper(II), nickel(II) and zinc(II) complexes with furanylmethyl- and thienylmethyl-dithiolenes: [1,3-dithiole-2-one and 1,3-dithiole-2-thione. Journal of Enzyme Inhibition and Medicinal Chemistry 21(6): 733-740.

Chohan, Z.H., Pervez, H., Rauf, A., Khan, K.M. & Supuran, C.T. 2004. Isatin-derived antibacterial and antifungal compounds and their transition metal complexes. Journal of Enzyme Inhibition and Medicinal Chemistry 19(5): 417-423.

Da Silva, J.F., Garden, S.J. & Pinto, A.C. 2001. The chemistry of isatins: A review from 1975 to 1999. Journal of the Brazilian Chemical Society 12(3): 273-324.

Dileepan, A.B., Prakash, T.D., Kumar, A.G., Rajam, P.S., Dhayabaran, V.V. & Rajaram, R. 2018. Isatin based macrocyclic Schiff base ligands as novel candidates for antimicrobial and antioxidant drug design: In vitro DNA binding and biological studies. Journal of Photochemistry and Photobiology B: Biology 183: 191-200.

Freeman, R.A. 1997. Hand Book of Nuclear Magnetic Resonance. 2nd ed. England: Longman Publishing.

Ganim, M.A., Baloglu, M.C., Aygun, A., Altunoglu, Y.C., Sayiner, H.S., Kandemirli, F. & Sen, F. 2019. Analysis of DNA protection, interaction and antimicrobial activity of isatin derivatives. International Journal of Biological Macromolecules 122: 1271-1278.

Geary, W.J. 1971. The use of conductivity measurements in organic solvents for the characterisation of coordination compounds. Coordination Chemistry Reviews 7(1): 81-122.

Gomathi, R.,   Ramu, A. & Murugan, A. 2014. Evaluation of DNA binding, cleavage, and cytotoxic activity of Cu(II), Co(II), and Ni(II) Schiff base complexes of 1-phenylindoline-2,3-dione with isonicotinohydrazide. Bioinorganic Chemistry and Applications 2014: Article ID. 215392.

Guo, H. 2019. Isatin derivatives and their anti-bacterial activities. European Journal of Medicinal Chemistry 164: 678-688.

Hanif, M. & Chohan, Z.H. 2013. Design, spectral characterization and biological studies of transition metal(II) complexes with triazole Schiff bases. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 104: 468-476.

Hyatt, J.L., Moak, T., Hatfield, M.J., Tsurkan, L., Edwards, C.C., Wierdl, M., Danks, M.K., Wadkins, R.M. & Potter, P.M. 2007. Selective inhibition of carboxylesterases by isatins, indole-2,3-diones. Journal of Medicinal Chemistry 50(8): 1876-1885.

Kumar, K., Liu, N., Yang, D., Na, D., Thompson, J., Wrischnik, L.A., Land, K.M. & Kumar, V. 2015. Synthesis and antiprotozoal activity of mono- and bis-uracil isatin conjugates against the human pathogen Trichomonas vaginalis. Bioorganic & Medicinal Chemistry 23(16): 5190-5197.

Lever, A.B.P. 1984. Inorganic Electronic Spectroscopy. New York: Elsevier.

Matesic, L., Locke, J.M., Vine, K., Ranson, M., Bremner, J.B. & Skropeta, D. 2012. Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2-diones, pyrrolo[3,2,1-ij]quinoline-1,2-diones and other polycyclic isatin derivatives. Tetrahedron 68: 6810-6819.

Moon, M.J., Lee, S.K., Lee, J.W., Song, W.K., Kim, S.W., Kim, J.I., Cho, C., Choi, S.J. & Kim, Y.C. 2006. Synthesis and structure-activity relationships of novel indirubin derivatives as potent anti-proliferative agents with CDK2 inhibitory activities. Bioorganic & Medicinal Chemistry 14(1): 237-246.

Muralisankar, M., Sujith, S., Bhuvanesh, N.S. & Sreekanth, A. 2016. Synthesis and crystal structure of new monometallic and bimetallic copper(II) complexes with N-substituted isatin thiosemicarbazone ligands: Effects of the complexes on DNA/protein-binding property, DNA cleavage study and in vitro anticancer activity. Polyhedron 118: 103-117.

Nair, M.S. & Joseyphus, R.S. 2008. Synthesis and characterization of Co(II), Ni(II), Cu(II) and Zn(II) complexes of tridentate Schiff base derived from vanillin and DL-alpha-aminobutyric acid. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy70(4): 749-753.

Nakamoto, K. 2009. Infrared Spectra of Inorganic and Coordination Compounds. 6th ed. New York: Wiley Interscience.

Nyquist, R.A. 2001. Interpreting Infrared, Raman, and Nuclear Magnetic Resonance Spectra. Massachusetts: Academic Press.

Pandeya, S.N., Smitha, S., Jyoti, M. & Sridhar, S.K. 2005. Biological activities of isatin and its derivatives. Acta Pharm 55(1): 27-46.

Pandeya, S.N., Sriram, D., Nath, G. & De Clercq, E. 2000. Synthesis, antibacterial, antifungal and antiviral activity evaluation of some new bis-Schiff bases of isatin and their derivatives. Arzneimittelforschung 50(1): 55-59.

Prakash, C.R. & Raja, S. 2011. Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) urea derivatives. European Journal of Medicinal Chemistry 46(12): 6057-6065.

Raghavendra, R., Reddy, K.R. & Mahendra, K.N. 2013. Synthesis, characterization and biological activities of a new 5-chloroisatin Schiff base and its metal complexes. Chemical Science Transactions 2(3): 1063-1069.

Rao, R., Reddy, K. & Mahendra, K. 2014. Synthesis, characterization and biological activities of a new 5-chloroisatin Schiff base and its metal complexes. Bulgarian Chemical Communications 46: 11-17.

Shakir, M., Bano, N., Rauf, M.A. & Owais, M. 2017. Pharmacologically significant tetraaza macrocyclic metal complexes derived from isatin and 3,4-diaminobenzophenone: synthesis, spectral studies and comparative in vitro biological assessment. Journal of Chemical Sciences 129(12): 1905-1920.

Sumrra, S.H., Atif, A.H., Zafar, M.N., Khalid, M., Tahir, M.N., Nazar, M.F., Nadeem, M.A. & Braga, A.A.C. 2018. Synthesis, crystal structure, spectral and DFT studies of potent isatin derived metal complexes. Journal of Molecular Structure 1166: 110-120.

Vine, K.L., Matesic, L., Locke, J.M., Ranson, M. & Skropeta, D. 2009. Cytotoxic and anticancer activities of isatin and its derivatives: A comprehensive review from 2000-2008. Anti-Cancer Agents in Medicinal Chemistry 9(4): 397-414.

Xu, Z., Zhang, S., Gao, C., Fan, J.,  Zhao, F., Lv, Z.S. & Freng, L.S. 2017. Isatin hybrids and their anti-tuberculosis activity. Chinese Chemical Letter 28(2): 159-167.

Yasmeen, S., Sumrra, S.H., Akram, M.S. & Chohan, Z.H. 2017. Antimicrobial metal-based thiophene derived compounds. Journal of Enzyme Inhibition and Medicinal Chemistry 32(1): 106-112.

Zhen, X., Peng Z., Zhao, S., Han, Y., Jin, Q. & Guan, L. 2015. Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-yl) acetamide derivatives. Acta Pharmaceutica Sinica 5(4): 343-349.

*Corresponding author; email: sajjadchemist@gmail.com