Generic placeholder image

Anti-Infective Agents

Author(s): Manoj Kumar*, Pallvi Aggarwal, Mehmet Varol, Shashi Sharma, Anita Rani, Zahoor Abbas, Vinit Prakash and Hardeep Singh Tuli*

DOI: 10.2174/2211352519666211104090749

DownloadDownload PDF Flyer Cite As
Synthesis, Spectral Investigations, Biological Potential and Molecular Docking Study of Novel Schiff Base and its Transition Metal Complexes

Article ID: e041121197661 Pages: 18

  • * (Excluding Mailing and Handling)

Abstract

Aim: The present study was designed to synthesize novel Schiff bases and their metal complexes with promising antimicrobial and anti-angiogenic potential.

Background: Currently, drug resistance has been seen in a diverse range of microbes, which is considered a major threat to widespread infectious diseases. Therefore, it is essential to investigate novel therapeutic molecules with broad-spectrum activities.

Methods: The novel Schiff base ligands were synthesized by using a condensation reaction of ethylenediamine with p-chloroacetanilide and p-bromoactanilide. Fe(III), Ni(II), Mn(II), and Co(II) metal complexes were prepared by refluxing the ligand with respective metal chloride salts in a 2:1 molar ratio.

Results: Structures of the synthesized compounds were characterized by IR, 1H NMR, UV-VIS, and mass spectrometry. Anti-microbial activities of all the synthesized compounds were determined against bacterial strains (S. aureus and K. pneumoniae) and fungal strains (A. niger and Trichophyton rubrum) by using the well plate diffusion method. DNA photo-cleavage and anti-angiogenic properties were evaluated by gel electrophoresis and CAM assay, respectively. Molecular docking studies were performed to analyze the binding interactions of synthesized compounds with topoisomerase II alpha.

Conclusion: The present preliminary efforts may be helpful to design novel drugs with therapeutic potential.

Keywords: Schiff bases, synthesis, characterization, antimicrobial, molecular docking, transition metal complexes.

Graphical Abstract

[1]
Abuamer, K.M.; Maihub, A.A.; El-Ajaily, M.M.; Etorki, A.M.; Abou-Krisha, M.M.; Almagani, M.A. The role of aromatic Schiff bases in the dyes techniques. International Journal of Organic Chemistry, 2014, 2014
[http://dx.doi.org/10.4236/ijoc.2014.41002]
[2]
Jia, A.Q.; Zhou, W.Y.; Wu, S.M.; Shi, H.T.; Zhang, Q.F. Cis‐Dioxo‐molybdenum (VI) Complexes with Diaminoguanidinium and Triaminoguanidinium Schiff Bases and Their Catalytic Application for Epoxidation of Cyclohexene. ChemistrySelect, 2020, 5(36), 11085-11095.
[http://dx.doi.org/10.1002/slct.202002938]
[3]
Vikneshvaran, S.; Velmathi, S. Schiff Bases of 2,5‐Thiophenedicarboxaldehyde as Corrosion Inhibitor for Stainless Steel under Acidic Medium: Experimental, Quantum Chemical and Surface Studies. ChemistrySelect, 2019, 4(1), 387-392.
[http://dx.doi.org/10.1002/slct.201803235]
[4]
Ahmed, D.S.; El-Hiti, G.A.; Hameed, A.S.; Yousif, E.; Ahmed, A. New tetra-Schiff bases as efficient photostabilizers for poly (vinyl chloride). Molecules, 2017, 22(9), 1506.
[http://dx.doi.org/10.3390/molecules22091506] [PMID: 28891944]
[5]
Alterhoni, E.; Tavman, A.; Gürbüz, D.; Hacioglu, M.; Çinarli, A.; Şahin, O.; Tan, A.S.B. Synthesis, Characterization and Antimicrobial Activity of Schiff Bases Including Three Hydroxy Groups and Their CoCl2, PdCl2, CuCl2 and ZnCl2 Complexes. ChemistrySelect, 2020, 5(31), 9730-9735.
[http://dx.doi.org/10.1002/slct.202001498]
[6]
Singh, G.; Kalra, P.; Arora, A.; Singh, A.; Sharma, G.; Maurya, I.K.; Dutta, S.; Munshi, P.; Verma, V. Acetylenic indole‐encapsulated schiff bases: Synthesis, in silico studies as potent antimicrobial agents, cytotoxic evaluation and synergistic effects. ChemistrySelect, 2018, 3(8), 2366-2375.
[http://dx.doi.org/10.1002/slct.201703018]
[7]
Wang, Y-Y.; Xu, F-Z.; Zhu, Y-Y.; Song, B.; Luo, D.; Yu, G.; Chen, S.; Xue, W.; Wu, J. Pyrazolo[3,4-d]pyrimidine derivatives containing a Schiff base moiety as potential antiviral agents. Bioorg. Med. Chem. Lett., 2018, 28(17), 2979-2984.
[http://dx.doi.org/10.1016/j.bmcl.2018.06.049] [PMID: 30122226]
[8]
Mahal, A.; Wu, P.; Jiang, Z.H.; Wei, X. Schiff bases of tetrahydrocurcumin as potential anticancer agents. ChemistrySelect, 2019, 4(1), 366-369.
[http://dx.doi.org/10.1002/slct.201803159]
[9]
Bano, B.; Khan, K.M.; Jabeen, A.; Hameed, A.; Faheem, A.; Taha, M.; Perveen, S.; Iqbal, S. Aminoquinoline Schiff Bases as Non‐Acidic, Non‐Steroidal, Anti‐Inflammatory Agents. ChemistrySelect, 2017, 2(31), 10050-10054.
[http://dx.doi.org/10.1002/slct.201702200]
[10]
Bakır, T.K.; Lawag, J.B. Preparation, characterization, antioxidant properties of novel Schiff bases including 5-chloroisatin-thiocarbohydrazone. Res. Chem. Intermed., 2020, 1-17.
[http://dx.doi.org/10.1007/s11164-020-04105-y]
[11]
Murtaza, S.; Akhtar, M.S.; Kanwal, F.; Abbas, A.; Ashiq, S.; Shamim, S. Synthesis and biological evaluation of schiff bases of 4-aminophenazone as an anti-inflammatory, analgesic and antipyretic agent. J. Saudi Chem. Soc., 2017, 21, S359-S372.
[http://dx.doi.org/10.1016/j.jscs.2014.04.003]
[12]
Aggarwal, S.; Paliwal, D.; Kaushik, D.; Gupta, G.K.; Kumar, A. Pyrazole Schiff base hybrids as anti-malarial agents: Synthesis, in vitro screening and computational study. Comb. Chem. High Throughput Screen., 2018, 21(3), 194-203.
[http://dx.doi.org/10.2174/1386207321666180213092911] [PMID: 29436997]
[13]
Koothappan, M.; Vellai, R.D.; Subramanian, I.P.; Pillai, S.; Pillai, S. Synthesis and evaluation of antidiabetic properties of a zinc mixed ligand complex in high-fat diet-low-dose streptozotocin-induced diabetic rats. Asian J. Pharm. Clin. Res., 2018, 11, 429-438.
[http://dx.doi.org/10.22159/ajpcr.2018.v11i5.24870]
[14]
Zhang, X.; Bi, C.; Fan, Y.; Cui, Q.; Chen, D.; Xiao, Y.; Dou, Q.P. Induction of tumor cell apoptosis by taurine Schiff base copper complex is associated with the inhibition of proteasomal activity. Int. J. Mol. Med., 2008, 22(5), 677-682.
[PMID: 18949390]
[15]
Arabahmadi, R. Cobalt(II) Complexes Derived from Azo‐Azomethine Ligands: Synthesis, Characterization, Solvatochromic, Fluorescence, Thermal, Electrochemical and Antimicrobial Properties. ChemistrySelect, 2019, 4(17), 4883-4891.
[http://dx.doi.org/10.1002/slct.201900075]
[16]
Omar, M.; Abd El‐Halim, H.F.; Khalil, E.A. Synthesis, characterization, and biological and anticancer studies of mixed ligand complexes with Schiff base and 2, 2′‐bipyridine. Appl. Organomet. Chem., 2017, 31(10), e3724.
[http://dx.doi.org/10.1002/aoc.3724]
[17]
Omidi, S.; Kakanejadifard, A. A review on biological activities of Schiff base, hydrazone, and oxime derivatives of curcumin. RSC Advances, 2020, 10(50), 30186-30202.
[http://dx.doi.org/10.1039/D0RA05720G]
[18]
Mostafa, MH, K.; Eman, H,I.; Gehad, G,M.; Ehab, M,Z.; Ahmed, B. Synthesis and characterization of a novel schiff base metal complexes and their application in determination of iron in different types of natural water. Open J. Inorg. Chem., 2012, 2012
[19]
Nagababu, P.; Kumar, D.A.; Reddy, K.L.; Kumar, K.A.; Mustafa, M.B.; Shilpa, M.; Satyanarayana, S. DNA Binding and Photocleavage Studies of Cobalt (III) Ethylenediamine Pyridine Complexes:[Co(en)2 (py)2]3. Metal-based drugs, 2008, 2008
[20]
Ahmed, N.; Riaz, M.; Ahmed, A.; Bhagat, M. Synthesis, characterisation, and biological evaluation of Zn (II) complex with tridentate (NNO Donor) schiff base ligand. Int. J. Inorg. Chem., 2015, 2015
[21]
Althaher, L.J. Synthesis and Characterization of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Hg(II) Complexes with [(N-(N-benzilidin aminoethyl) Iodomethylene Dithiocarbamate]. Rafidain j. sci., 2013, 24(4), 25-33.
[22]
ter Laak, E.A.; Noordergraaf, J.H.; Verschure, M.H. Susceptibilities of Mycoplasma bovis, Mycoplasma dispar, and Ureaplasma diversum strains to antimicrobial agents in vitro. Antimicrob. Agents Chemother., 1993, 37(2), 317-321.
[http://dx.doi.org/10.1128/AAC.37.2.317] [PMID: 8452363]
[23]
Pal, R.; Kumar, V.; Gupta, A.; Beniwal, V. Synthesis, characterization and DNA photocleavage study of a novel dehydroacetic acid based hydrazone Schiff’s base and its metal complexes. Med. Chem. Res., 2014, 23(7), 3327-3335.
[http://dx.doi.org/10.1007/s00044-014-0911-6]
[24]
Asha, M.S. Synthesis, characterization, thermal, anticancer and dna bindingproperties of Co(II), Ni(II), Cu(II), Cd(II) and Zn(II) complexes with schiff base. Int. J. Med. Pharm. Sci., 2014, 4(3), 41-52.
[25]
Patel, V.; Trivedi, P.; Gohel, H.; Khetani, D. Synthesis and Characterization of Schiff Base of p-chloro aniline and their Metal Complexes and their evaluation for Antibacterial Activity. Int. J. Adv. Pharmacy. Biol. Chem., 2014, 3, 999-1003.
[26]
Munjal, M. Synthesis, characterization and Antifungal activity of transition metal (II) complexes of Schiff base derived from p-amino acetanilide and salicylaldehyde. J. Pharmacogn. Phytochem., 2018, 7(6), 864-866.
[27]
Ghaidan, A.F.; Faraj, F.L.; Abdulghany, Z.S. Synthesis, Characterization and Cytotoxic Activity of new Indole Schiff Bases Derived from 2-(5-Chloro-3,3-Dimethyl-1,3-Dihydro-Indol-2-Ylidene)-Malonaldehyde with Aniline Substituted. Orient. J. Chem., 2018, 34(1), 169-181.
[http://dx.doi.org/10.13005/ojc/340119]
[28]
Pandya, J.H.; Jadeja, R.N.; Ganatra, K.J. Spectral characterization and biological evaluation of Schiff bases and their mixed ligand metal complexes derived from 4, 6-diacetylresorcinol. J. Saudi Chem. Soc., 2014, 18(3), 190-199.
[http://dx.doi.org/10.1016/j.jscs.2011.06.010]
[29]
Ibrahim, A.; Yusuf, B.; Hamisu, A. Synthesis, characterization and antimicrobial studies of Cu(II) and Zn(II) complexes with the Schiff base N-salicylidene-4-chloroaniline. ChemSearch J., 2017, 8(2), 68-74.
[30]
Berradj, O.; Adkhis, A.; Bougherra, H.; Bruno, G.; Michaud, F. Synthesis, spectroscopy, crystal structure and DFT studies of cobalt(III) complexes featuring dimethylglyoximate and aniline or p-bromoaniline ligands. J. Mol. Struct., 2017, 1131, 266-274.
[http://dx.doi.org/10.1016/j.molstruc.2016.11.058]
[31]
Ambika, S.; Manojkumar, Y.; Arunachalam, S.; Gowdhami, B.; Meenakshi Sundaram, K.K.; Solomon, R.V.; Venuvanalingam, P.; Akbarsha, M.A.; Sundararaman, M. Biomolecular interaction, anti-cancer and anti-angiogenic properties of cobalt(III) Schiff base complexes. Sci. Rep., 2019, 9(1), 2721.
[http://dx.doi.org/10.1038/s41598-019-39179-1] [PMID: 30804454]
[32]
Thrilochana, P.; Nimain, C.; Kuntal, H.; Ramachandran, S. Synthesis and biological evaluation of new Thiadiazole analogues for anti-diabetic activity against Alloxan induced diabetes. J. Pharm. Res., 2014, 8, 1559-1562.
[33]
Mandewale, M.C.; Thorat, B.R.; Shelke, D.; Yamgar, R. Fluorescence and molecular docking studies of some new Schiff bases of 6-chloro-2-hydroxyquinoline-3-carbaldehyde. J. Chem. Pharm. Res., 2015, 7(6), 900-909.
[34]
Cianga, I.; Ivanoiu, M. Synthesis of poly (Schiff-base)s by organometallic processes. Eur. Polym. J., 2006, 42(8), 1922-1933.
[http://dx.doi.org/10.1016/j.eurpolymj.2006.03.001]
[35]
Rathore, K.; Singh, R.K.; Singh, H. Structural, spectroscopic and biological aspects of O, N-donor Schiff base ligand and its Cr(III), Co(II), Ni(II) and Cu(II) complexes synthesized through green chemical approach. E-J. Chem., 2010, 7.
[http://dx.doi.org/10.1155/2010/521843]
[36]
Nasir Uddin, M.; Chowdhury, D.; Hossain, K. Titanium(IV) Complexes of Unsymmetrical Schiff Bases Derived from Ethylenediamine and o‐Hydroxyaldehyde/Ketone and Their Anti‐microbial Evaluation. J. Chin. Chem. Soc. (Taipei), 2012, 59(12), 1520-1527.
[http://dx.doi.org/10.1002/jccs.201200169]
[37]
Riswan Ahamed, M.A.; Azarudeen, R.S.; Kani, N.M. Antimicrobial applications of transition metal complexes of benzothiazole based terpolymer: Synthesis, characterization, and effect on bacterial and fungal strains. Bioinorg. chem. appl., 2014, 2014
[http://dx.doi.org/10.1155/2014/764085]
[38]
Methaq, S. Some transition metal complexes with new Schiff base ligand hexadentate. Acta Chim. Pharm. Indica, 2013, 3(2), 140-148.
[39]
Thalavaipandian, A.S.; Natarajan, R.; Baskaran, T. Synthesis, characterization and Antifungal activity of transition metal (II) complexes of Schiff base derived from p-aminoacetanilide and salicylaldehyde. Int. J. Curr. Res., 2017, 3, 1253-1260.
[40]
Ommenya, F.; Nyawade, E.; Andala, D.; Kinyua, J. Synthesis, Characterization and Antibacterial Activity of Schiff Base, 4-Chloro-2-{(E)-[(4-Fluorophenyl) imino] methyl} phenol Metal (II) Complexes. J. Chem., 2020, 2020
[41]
George Lukosea, K.M.; Sajua, S.; Rahima, S. Synthesis and structural characterization studies of cobalt(III), manganese(III)and iron(III) schiff base complexes. J. Chem. Pharm. Res., 2013, 5(5), 241-249.
[42]
Fair, R.J.; Tor, Y. Antibiotics and bacterial resistance in the 21st century. Perspectives medl chem., 2014, 6, 25-64.
[43]
Davies, J.; Davies, D. Origins and evolution of antibiotic resistance. Microbiol. Mol. Biol. Rev., 2010, 74(3), 417-433.
[http://dx.doi.org/10.1128/MMBR.00016-10] [PMID: 20805405]
[44]
Saddam Hossain, Md. A short review on antimicrobial activity study on transition metal complexes of Ni incorporating schiff bases. Adv. technol. sci., 2019, 2(1), 1-16.
[45]
Chaudhary, N.K.; Mishra, P. Metal complexes of a novel Schiff base based on penicillin: characterization, molecular modeling, and antibacterial activity study. Bioinorg. Chem. Appl., 2017, 2017
[http://dx.doi.org/10.1155/2017/6927675]
[46]
Fonkui, T.Y.; Ikhile, M.I.; Ndinteh, D.T.; Njobeh, P.B. Microbial activity of some heterocyclic Schiff bases and metal complexes: A review. Trop. J. Pharm. Res., 2018, 17(12), 2507-2518.
[http://dx.doi.org/10.4314/tjpr.v17i12.29]
[47]
Saranya, J.; Kirubavathy, S.J.; Chitra, S.; Zarrouk, A.; Kalpana, K.; Lavanya, K.; Ravikiran, B. Tetradentate schiff base complexes of transition metals for antimicrobial activity. Arab. J. Sci. Eng., 2020, 1-13.
[48]
Divya, K.; Pinto, G.M.; Pinto, A.F. Application of metal complexes of Schiff bases as an antimicrobial drug: a review of recent works. Int. J. Curr. Pharm. Res., 2017, 9(3), 27-30.
[http://dx.doi.org/10.22159/ijcpr.2017.v9i3.19966]
[49]
More, M.S.; Joshi, P.G.; Mishra, Y.K.; Khanna, P.K. Metal complexes driven from Schiff bases and semicarbazones for biomedical and allied applications: a review. Mater. Today Chem., 2019, 14, 100195.
[http://dx.doi.org/10.1016/j.mtchem.2019.100195] [PMID: 32289101]
[50]
Nazirkar, B.; Mandewale, M.; Yamgar, R. Synthesis, characterization and antibacterial activity of Cu (II) and Zn (II) complexes of 5-aminobenzofuran-2-carboxylate Schiff base ligands. J. Taibah Univ. Sci., 2019, 13(1), 440-449.
[http://dx.doi.org/10.1080/16583655.2019.1592316]
[51]
Login, C.C.; Bâldea, I.; Tiperciuc, B.; Benedec, D.; Vodnar, D.C.; Decea, N.; Suciu, Ş. A novel thiazolyl schiff base: Antibacterial and antifungal effects and in vitro oxidative stress modulation on human endothelial cells. Oxid. med. cell. long., 2019, 2019
[52]
Singh, E.K. Synthesis, Characterisation and Antimicrobial Activity of Some Schiff Base Metal Chelates. J. Chem. Pharm. Res., 2017, 9(4), 180-184.
[53]
Matar, S.A.; Talib, W.H.; Mustafa, M.S.; Mubarak, M.S.; AlDamen, M.A. Synthesis, characterization, and antimicrobial activity of Schiff bases derived from benzaldehydes and 3, 3′-diaminodipropylamine. Arab. J. Chem., 2015, 8(6), 850-857.
[http://dx.doi.org/10.1016/j.arabjc.2012.12.039]
[54]
Watson, H. Structure and organization of membranesMembranes are composed of lipids, proteinsand sugars. Essays Biochem., 2015, 59, 43-70.
[http://dx.doi.org/10.1042/bse0590043] [PMID: 26504250]
[55]
Rahaman, F.; Mruthyunjayaswamy, B. Synthesis, spectral characterization and biological activity studies of transition metal complexes of Schiff base ligand containing indole moiety. Complex Metals, 2014, 1(1), 88-95.
[http://dx.doi.org/10.1080/2164232X.2014.889580]
[56]
Dhahagani, K.; Mathan Kumar, S.; Chakkaravarthi, G.; Anitha, K.; Rajesh, J.; Ramu, A.; Rajagopal, G. Synthesis and spectral characterization of Schiff base complexes of Cu(II), Co(II), Zn(II) and VO(IV) containing 4-(4-aminophenyl)morpholine derivatives: antimicrobial evaluation and anticancer studies. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2014, 117, 87-94.
[http://dx.doi.org/10.1016/j.saa.2013.07.101] [PMID: 23985482]
[57]
Chandra, S.; Tyagi, M. Ni(II), Pd(II) and Pt(II) complexes with ligand containing thiosemicarbazone and semicarbazone moiety: synthesis, characterization and biological investigation. J. Serb. Chem. Soc., 2008, 73(7), 727-734.
[http://dx.doi.org/10.2298/JSC0807727C]
[58]
Alias, M.; Kassum, H.; Shakir, C. Synthesis, physical characterization and biological evaluation of Schiff base M(II) complexes. J. Associ. Arab Uni. Basic App. Sci., 2014, 15, 28-34.
[59]
Kaushal, R.; Thakur, S. Syntheses and biological screening of schiff base complexes of titanium (IV). Chem. Eng. Trans., 2013, 32, 1801-1806.
[60]
Kondaiah, S.; Reddy, G.N.R.; Rajesh, D.; Joseph, J. Synthesis, characterization, and antibacterial activity of the schiff base derived from P-toluic hydrazide and O-vanilin (OVPTH Ligand) and its Mn(II), Co(II), Ni(II) and Cu(II) complexes. Indian J. Adv. Chem. Sci., 2013, 1(4), 228-235.
[61]
Chityala, V.K.; Kumar, S.K.; Macha, R.; Tigulla, P. DNA cleavage, cytotoxic activities, and antimicrobial studies of ternary copper(II) complexes of isoxazole Schiff base and heterocyclic compounds. Bioinorg. chem. app., 2014, 2014
[62]
Lunagariya, M.V.; Thakor, K.P.; Waghela, B.N.; Vaidya, F.U.; Pathak, C.; Patel, M.N. Design, synthesis, MTT assay, DNA interaction studies of platinum(II) complexes. J. Biomol. Struct. Dyn., 2018, 36(1), 14-31.
[http://dx.doi.org/10.1080/07391102.2016.1268071] [PMID: 27917701]
[63]
Kumar, MY.; Ambika, S.; Arulkumar, R.; Gowdhami, B.; Balaji, P.; Arunachalam, S.; Venuvanalingam, P.; Thirumurugan, R.; Akbarsha, M.A. Synthesis, DNA and BSA binding, in vitro anti-proliferative and in vivo anti-angiogenic properties of some cobalt (III) Schiff base complexes. New J. Chem., 2019, 43(28), 11391-11407.
[http://dx.doi.org/10.1039/C9NJ01269A]
[64]
Yadamani, S.; Neamati, A.; Homayouni-Tabrizi, M.; Yadamani, S.; Javdani-Mallak, A.; Beyramabadi, S.A. Anticancer Activities of Cu(II) Complex-Schiff Base and Low-Frequency Electromagnetic Fields and the Interaction Between Cu(II) Complex-Schiff Base with Bovine Serum Albumin by Spectroscopy. Appl. Biochem. Biotechnol., 2020, 190(3), 997-1009.
[http://dx.doi.org/10.1007/s12010-019-03118-7] [PMID: 31650355]
[65]
Kumar, A.; Singh, U.K.; Gupta, P.; Muzaffar, F.; Pathak, P.; Tomar, P. In synthesis, molecular docking and evaluation of antiangiogenic activity and cellular metastasis potential of some triazine and pyrrolidin-2-one derivatives. Pharma Chem., 2016, 8(10), 259-273.
[66]
Jadhav, A.K.; Karuppayil, S.M. Molecular docking studies on thirteen fluoroquinolines with human topoisomerase II a and b. In Silico Pharmacol., 2016, 5(1), 4.
[http://dx.doi.org/10.1007/s40203-017-0024-2] [PMID: 28667488]