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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Review Article

Schiff Bases and their Metal Complexes as Potential Anticancer Candidates: A Review of Recent Works

Author(s): Kirubel T. Tadele* and Tilahun W. Tsega

Volume 19, Issue 15, 2019

Page: [1786 - 1795] Pages: 10

DOI: 10.2174/1871520619666190227171716

Price: $65

Abstract

Background: Schiff bases and their metal complexes are emerging as key classes of medicinal compounds, possessing an enormous potential of biological activities like anticancer, anticonvulsant and antioxidant etc. The aim of this review is to examine the anticancer activity of different classes of Schiff bases and their metal complexes.

Methods: Anticancer activity of the already synthesized as well as the novel Schiff bases and their metal complexes was studied using different assays such as 3- [4,5-dimethyltiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT), PI staining, Sulforhodamine, Allium cepa, Sulfo- Rhodamine-B-stain(SRB), viability and potato disc against various human and animal cancer cell lines.

Results: The test results indicated significant differences in anticancer activity between subclasses of Schiff base compounds as well as between the Schiff base ligands and their metal complexes. Quinazolines showed a very high activity against HepG2 and MCF-7 cell lines. Pyrazole-naphthalene derivatives exhibited high activity against numerous carcinoma cells while [Ni(HL1)2(OAc)2] showed the highest. Azosal and its tin(IV) complexes displayed high activity against U-1242 MG and excellent activity against HCT-116 cell lines. 2-thiouracil sulfonamides displayed high activity against MCF7, CaCo-2 carcinoma cells. Vitamin-B6 and its oxovanadium complex showed good activity against MCF-7, 3T3 and cervical cancer HeLa cancer cell lines in the presence of visible light. Indoles displayed high activity against AMJ13. Porphyrines derivatives exhibited good activity while its binuclear(Y and K) complexes displayed high activity against several carcinoma cells. Chitosan complexes of [Pd(II) and Pt(II)] showed a very high anticancer activity against MCF-7 carcinoma cell.

Conclusion: Schiff bases possess a high potential to inhibit carcinoma cells which enhanced with complexation, but the mechanism of their antitumor activity is still doubt.

Keywords: Schiff bases, metal complexes, anticancer activity, MTT assay, quinazolines, indoles.

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[1]
Walaa, H.M.; Reem, G.D.; Gehad, G.M. Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis, spectroscopic, thermal analysis, antimicrobial and in vitro anticancer activity. Appl. Organomet. Chem., 2016, 30, 221-230.
[2]
Jin, V.X.; Tan, S.I.; Ranford, J.D. Platinum(II) triammine antitumour complexes: Structure-activity relationship with guanosine 5 '-monophosphate (5 '-GMP). Inorg. Chem. Acta, 2005, 358, 677-686.
[3]
Ashu, C.; Anshul, S. Schiff bases: An emerging potent class of pharmaceuticals. Int. J. Curr. Res. Med. Sci, 2017, 3, 60-74.
[4]
Abu-Dief, A.M.; Mohamed, I.M.A. A review on versatile applications of transition metal complexes incorporating Schiff bases. Beni-Suef Univ. J. Basic Appl. Sci., 2015, 4, 119-133.
[5]
Spinu, C.; Kriza, A. Co(II), Ni(II) and Cu(II) complexes of bidentate Schiff bases. Acta Chim. Slov., 2000, 47, 179-185.
[6]
Zoubi, W.A. Biological activities of schiff bases and their complexes: A review of recent works. Int. J. Org. Chem., 2013, 3, 73-95.
[7]
Ejidike, I.P.; Ajibade, P.A. Synthesis, characterization and biological studies of metal(II) complexes of (3e)-3-[(2-(e)-[1-(2,4-dihydroxyphenyl) ethylidene]aminoethyl)imino]-1-phenylbutan-1-one Schiff base. Molecules, 2015, 20(6), 9788-9802.
[8]
Da Silva, C.M.; da Silva, D.L.; Modolo, L.V.; Alves, R.B.; de Resende, M.A.; Martins, C.V.B.; de Fátima, A. Schiff bases: A short review of their antimicrobial activities. J. Adv. Res., 2011, 2, 1-8.
[9]
Qin, W.; Long, S.; Panunzio, M.; Biondi, S. Schiff Bases: A short survey on an evergreen chemistry tool. Molecules, 2013, 18, 12264-12289.
[10]
Kajal, A.; Bala, S.; Kamboj, S.; Sharma, N.; Saini, V. Schiff bases: A versatile pharmacophore. J. Catal., 2013, 2013, 1-14.
[11]
Shagufta, S.; Irash, A. An insight into the therapeutic potential of quinazoline derivates as anticancer agents. MedChemComm, 2017, 8, 871-885.
[12]
Cancer facts and figure. 2017, Available from: https://www. cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html
[13]
Babasaheb, P.B.; Shrikant, S.G.; Ragini, G.B.; Jalinder, V.T.; Chandrahas, N.K. Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, anti-inflammatory and antioxidant agents. Bioorg. Med. Chem., 2010, 18, 1364-1370.
[14]
Baselga, J.; Swain, S.M. Novel anticancer targets: Revisiting ERBB2 and discovering ERBB3. Nat. Rev. Cancer, 2009, 9, 463-475.
[15]
Brown, C.H.J.; Lain, S.; Verma, C.H.S.; Fersht, A.R.; Lane, D.P. Awakening guardian angels: Drugging the p53 pathway. Nat. Rev. Cancer, 2009, 9, 862-873.
[16]
Semenza, G.L. Hypoxia and cancer. Cancer Metastasis Rev., 2007, 26, 223-224.
[17]
Hanif, M.; Babak, M.V.; Hartinger, C.G. Development of anticancer agents: wizardry with osmium. Drug Discov. Today, 2014, 19, 1640-1648.
[18]
Abu-Surrah, A.S.; Kettunen, M. Platinum group antitumor chemistry: design and development of new anticancer drugs complementary to cisplatin. Curr. Med. Chem., 2006, 13, 1337-1357.
[19]
Lease, N.; Vasilevski, V.; Carreira, M.; de Almeida, A.; Sanaú, M.; Hirva, P.; Casini, A.; Contel, M. Potential anticancer heterometallic Fe-Au and Fe-Pd agents: initial mechanistic insights. J. Med. Chem., 2013, 56, 5806-5818.
[20]
Jamaludin, N.S.; Goh, Z.J.; Cheah, Y.K.; Ang, K.P.; Sim, J.H.; Khoo, C.H.; Fairuz, Z.A.; Halim, S.N.; Ng, S.W.; Seng, H.L.; Tieknk, E.R. Phosphanegold(I)dithiocarbamates,R3PAu[SC(=S)N((i) Pr)CH2CH2OH] for R = Ph, Cy and Et: Role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways. Eur. J. Med. Chem., 2013, 67, 127-141.
[21]
Hu, C.; Li, X.; Wang, W.; Zhang, R.; Deng, L. Metal-N-heterocyclic carbene complexes as anti-tumor agents. Curr. Med. Chem., 2014, 21, 1220-1230.
[22]
Au-Yeung, S.C.F.; Pang, P.S.K.; Ho, Y.P. Innovative platinum derived anticancer agents-risk or opportunity? Nat. Rev. Drug Discov., 2006, 5, 1.
[23]
Wheate, N.J.; Walker, S.; Craig, G.E.; Oun, R. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans., 2010, 39, 8113-8127.
[24]
Ahmed, M.A.; Ibrahim, M.A. A review on versatile applications of transition metal complexes incorporating Schiff bases. J. Basic Appl. Sci., 2015, 4, 119-133.
[25]
Salerno, S.; Da Settimo, F.; Taliani, S.; Simorini, F.; La Motta, C.; Fornaciari, G.; Marini, A.M. Recent advances in the development of dual Topoisomerase I and II inhibitors as anticancer drugs. Curr. Med. Chem., 2010, 17, 4270-4290.
[26]
De Vita, J.; Samuel, V.T.; Steven, H. Cancer e principles and practice of oncology, 7th ed; NewYork: Lippincott Williams & Wilkins, 2005.
[27]
Thomas, P.S.; Vinay, K., Eds.; Robbins basic pathology, 8th ed; Saunders: Philadelphia, 2007.
[28]
Al-Shamary, D.S.; Al-Alshaikh, M.A.; Kheder, N.A.; Mabkhot, Y.N.; Badshah, S.L. Molecular docking and biological evaluation of some thioxoquinazolin-4(3H)- one derivatives as anticancer, antioxidant and anticonvulsant agents. Chem. Cent. J., 2017, 11, 48.
[29]
Mossman, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65, 55-63.
[30]
Hui, Y.; Wei, Z.; Qing, Y.; Fu-Ping, H.; He-Dong, B.; Hong, L. Ni(II) Complexes with schiff base ligands: Preparation, characterization, DNA/Protein interaction and cytotoxicity studies. Molecules, 2017, 22(10), 3-10.
[31]
Xiao, Y-J.; Diao, Q-C.; Liang, Y-H.; Zeng, K. Two novel Co(II) complexes with two different Schiff bases: Inhibiting growth of human skin cancer cells. Braz. J. Med. Biol. Res., 2017, 50, 1-5.
[32]
Jacqueline, K.B.; Brian, M.Z.; Valerie, C.P. Metallointercalators and metalloinsertors. Chem. Commun., 2007, 44, 4565-4579.
[33]
Kavitha, A.; Anandhavelu, S.; Easwaramoorthy, D.; Karuppasamy, K.; Hyun-Seok, K.; Dhanasekaran, V. In vitro cytotoxicity activity of novel Schiff base ligand-lanthanide complexes. Sci. Rep., 2018, 8, 2-8.
[34]
El-Kholy, N.G. Synthesis, Spectroscopic characterization, Antimicrobial, Antitumor Properties of new 4-amino-2,3 dimethyl-1-phenyl -3- pyrazolone-5-one (antipyrine) Schiff Bases and its transition metal complexes. J. Am. Sci., 2017, 13, 133-143.
[35]
Brindha, G.; Vijayanthimala, R. Mixed ligand complexes of Copper(II), Nickel(II) and Zinc(II) with salicylaldehyde tyrosine Schiff base and dimethylaminopyridine/ dimethylaminopyridine and Phenanthroline - Synthesis, spectral characterization and biological studies. Res. J. Pharm. Biol. Chem. Sci., 2017, 8, 930-936.
[36]
Muthusamy, S.; Natarajan, R. Pharmacological activity of a few transition metal complexes: A short review. J. Chem. Biol. Ther., 2016, 1, 108.
[37]
Redouane, T.; Nassera, T.; Christian, G.; Embarek, B.; Laurent, D. Progress in copper complexes as anticancer agents. Med. Chem., 2017, 7, 875-879.
[38]
Brindha, G.; Vijayanthimala, R. Complexes of copper (II) with thiosemicarbazone and chloroethanol-synthesis, characterization and biological studies. IOSR J. App. Chem, 2016, 9, 90-93.
[39]
Heng, L.; Yu-Fen, X.; Bao-Fei, S.; Li-Rong, H.; Xing-Hui, W.; Hua-Yong, L.; Xu-Hui, Z.; Wei-Dong, P.; Xiao-Dong, Z. Synthesis and evaluation of in vitro antibacterial and antitumor activities of novel N,N-disubstituted schiff bases. Biochem. Res. Int., 2017, 20176257240
[40]
Ikechukwu, P.E.; Peter, A.A. Synthesis, characterization, anticancer, and antioxidant studies of Ru(III) complexes of monobasic tridentate schiff bases. Bioinorg. Chem. Appl., 2016, 2016, 1-11.
[41]
Sava, G.; Zorzet, S.; Giraldi, T.; Mestroni, G.; Zassinovich, G. Antineoplastic activity and toxicity of an organometallic complex of ruthenium(II) in comparison with cis-PDD in mice bearing solid malignant neoplasms. Eur. J. Cancer Clin. Oncol., 1984, 20, 841-847.
[42]
Sava, G.; Bergamo, A. Ruthenium-based compounds and tumour growth control. Int. J. Oncol., 2000, 17, 353-365.
[43]
Izet, E.; Emira, K.; Aner, M.; Emir, T.; Dzenana, K.; Adnan, Z.; Zana, D. Cytogenotoxic effects of two potential anticancer Ruthenium(III) Schiff Bases complexes. J. Hear. Sci., 2016, 6, 112-120.
[44]
Brabec, V.; Novakova, O. DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity. Drug Resist. Updat., 2006, 9, 111-122.
[45]
Menezes, C.S.; de Paula Costa, L.C.; de Melo Rodrigues Avila, V.; Ferreira, M.J.; Vieira, C.U.; Pavanin, L.A. Analysis in vivo of antitumor activity, cytotoxicity and interaction between plasmid DNA and the cis-dichloro-tetra-amine-ruthenium(III) chloride. Chem. Biol. Interact., 2007, 167, 116-124.
[46]
Hazarika, P.; Bezbaruah, B.; Deka, J.; Deka, R.P.; Medhi, O.K.; Medhi, C. The features of protein binding by ruthenium complexes: Docking, force field and QM/MM studies. IJRRAS, 2013, 14, 64-74.
[47]
Kratz, F.; Hartmann, M.; Keppler, B.; Messori, L. The binding properties of two antitumor ruthenium(III) complexes to apotransferrin. J. Biol. Chem., 1994, 269, 2581-2588.
[48]
Ljubijankić, N.; Zahirović, A.; Turkušić, E.; Kahrović, E. DNA binding properties of two Ruthenium(III) complexes containing Schiff bases derived from salicylaldehyde: Spectroscopic and electrochemical evidence of CT DNA intercalation. Croat. Chem. Acta, 2013, 86, 215-222.
[49]
Kahrović, E.; Bektaš, S.; Turkušić, E.; Zahirović, A. Evidence on antimicrobial activity of Sodium dichloro-bis[N-phenyl-5-chlorosalicylideneiminato-N,O]ruthenate(III) against gram positive bacteria. SYLWAN, 2014, 158, 482-493.
[50]
Williams, J.L.; Lewis-Alleyne, L.C.; Solomon, M.; Nguyen, L.; Johnson, R.; Vital, J.; Ji, P.; Durant, J.; Cooper, C.; Cagle, P.; Martin, P.; VanDerveer, D.; Jarrett, W.L.; Holder, A.A. An in vitro study on the effect of synthesized tin(IV) complexes on glioblastoma, colorectal, and skin cancer cell lines. Biomed. Res. Clin. Pra, 2016, 1, 7-15.
[51]
Jing, X.; Shanshan, S.; Ruhua, C.; Jun, X.; Kun, D.; Jiancui, H.; Qin, L.; Wenjiao, Z.; Tieliang, M.A.; Lei, J.I.A.; Hongxin, C.A.I.; Taofeng, Z.H.U. Synthesis, characterization and antitumor activity of Ln(III) complexes with hydrazone Schiff base derived from 2-acetylpyridine and isonicotinohydrazone. Oncol. Lett., 2017, 13, 4413-4419.
[52]
Zeinab, A.M.; Mastoura, M.E.; Rasha, A.M.; Faty, S.M.; Gomha, S.S.A.; Yahia, N.M. Synthesis, antitumor evaluation and molecular docking of new morpholine based heterocycles. Molecules, 2017, 22, 1211.
[53]
da Silva, C.M.; Silva, M.M.; Reis, F.S.; Ruiz, A.T.G.; de Carvalho, J.E.; Santos, J.C.C.; Figueiredo, I.M.; Alves, R.B.; Modoloe, L.V.; de Fátima, Â. Studies on free radical scavenging, cancer cell antiproliferation and calf thymus DNA interaction of Schiff bases. J. Photochem. Photobiol., 2017, 172, 129-138.
[54]
Arun, K.; Samya, B.; Sanjoy, M.; Akhil, R.C. Vitamin-B6 Schiff base dioxovanadium(V) complex for targeted visible light-induced anticancer activity. Indian J. Chem., 2017, 56, 806-813.
[55]
Wang, F-Y.; Tang, X-M.; Wang, X.; Huang, K-B.; Feng, H-W.; Chen, Z-F.; Liu, Y-N.; Liang, H. Mitochondria-targeted platinum(II) complexes induce apoptosis-dependent autophagic cell death mediated by ER-stress in A549 cancer cells. Eur. J. Med. Chem., 2018, 155, 639-650.
[56]
Awad, S.M.; Ahmed, N.M.; Haffez, H.R. Synthesis, anticancer activity and molecular docking study of some novel 2-thiouracil sulfonamide derivatives. Pharmacophore, 2018, 9, 30-41.
[57]
Vichai, V.; Kirtikara, K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat. Protoc., 2006, 1, 1112-1116.
[58]
El-Tabl, A.S.; Mohamed, A.M.; Wahba, M.A.; Abd El-Halim, A.N. Synthesis, characterization, and anticancer activity of new metal complexes derived from 2-hydroxy-3-(hydroxyimino)-4-oxopentan-2-ylidene) benzohydrazide. Bioinorg. Chem. Appl., 2015, 2015126023
[59]
Abdou, S.; El-Tabl, M.M.; Abd-El, W.; Mohammed, H.; Abu-Setta, H. Metallo- bioactive compounds as potential novel anticancer therapy. Int. J. Adv. Chem, 2018, 4, 17-37.
[60]
Ghaidan, F.L.F.; Aseel, F.; Zaynab, S.A. 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 substituted aniline. Orient. J. Chem., 2018, 34, 169-181.
[61]
Mello-Andrade, F.; da Costa, W.L.; Pires, W.C.; Pereira, F.C.; Cardoso, C.G.; Lino-Junior, R.S.; Irusta, V.R.C.; Carneiro, C.C.; de Melo-Reis, P.R.; Castro, C.H.; Almeida, M.A.P.; Batista, A.A.; Silveira-Lacerda, E.P. Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression. Tumour Biol., 2017, 39(10), 1-18.
[62]
Jagadish, T.; Satyanarayana, B. Anticancer, DNA cleavage and docking studies of metal(II) complexes with imine base (E)-N-((1H-Imidazol-2-Yl) methylene)-benzo(D)thiazol-2amine. Int. J. Eng. Tech. Sc. Res, 2018, 5, 496-505.
[63]
Zhang, Y.S.; Liu, J.C.; Gu, J.J. Synthesis, crystal structure, and anti-breast cancer activity of a novel metal-porphyrinic complex [YK(TCPP)(OH)2. (solvents)x]. Braz. J. Med. Biol. Res., 2018, 51, 1414-1431.
[64]
Chang, H.Q.L.; Jia, J.X.; Zhu, T.F.; Xu, Z.Q.; Chen, R.H.; Ma, T.L.; Wang, Y.; Wu, W.N. Syntheses, crystal structures, anticancer activities of three reduce Schiff base ligand based transition metal complexes. Molec. Struc, 2016, 1106, 366-372.
[65]
Suyue, P.; Guohu, W.; Bo, Z.; Guoqiang, W.; Shixiong, H. Two novel Ni (II) complexes with two different Schiff bases: Inhibiting glioma cells growth. Biomed. Res., 2017, 28, 2526-2529.
[66]
Palanimurugan, A.; Kulandaisamy, A. Synthesis, characterization,antimicrobial and anticancer activities 14-membered macrocyclic Schiff bases metal complexes. Asian J. Chem., 2018, 30, 1262-1268.
[67]
Křikavová, R.; Vančo, J.; Trávníček, Z.; Hutyra, J.; Dvořák, Z. Design and characterization of highly in vitro antitumor active ternary copper(II) complexes containing 2′-hydroxychalcone ligands. J. Inorg. Biochem., 2016, 163, 8-17.
[68]
Abd El-Halim, H.F.; Mohamed, G.G.; Anwar, M.N. Antimicrobial and anticancer activities of Schiff base ligand and its transition metal mixed ligand complexes with heterocyclic base. Appl. Organomet. Chem., 2017, 32, 3899.
[69]
Dilshad, E.; Mirza, B.; Shabbir, M.; Haq, Z.; Akhter, Z. Biological evaluation of azaheterocyclic derivatives and their intermediates. World J. Pharm. Res, 2014, 3, 2111-2126.
[70]
Coker, P.S.; Radecke, J.; Guy, C.; Camper, N.D. Potato disc tumor induction assay: A multiple mode of drug action assay. Phytomedicine, 2003, 10(2-3), 133-138.
[71]
Ferrigni, N.R.; Putnam, J.E.; Anderson, B.; Jacobsen, L.B.; Nichols, D.E.; Moore, D.S.; McLaughlin, J.L.; Powell, P.G.; Smith, C.R.J. Modification and evaluation of the potato disc assay and antitumor screening of Euphorbiacae seeds. J. Nat. Prod., 1982, 45, 679-686.
[72]
Sobola, A.O.; Watkins, G.M.; Van Brecht, B. Synthesis, characterization and antimicrobial activity of copper(II) complexes of some ortho-substituted an-iline Schiff bases; crystal structure of bis (2-methoxy-6-imino) methyl phenol copper(II) complex. S. Afr. J. Chem., 2014, 67, 45-51.
[73]
Dilshad, E.; Mirza, B.; Shabbir, M.; Haq, Z.; Akhter, Z. Biological evaluation of aza-heterocyclic derivatives and their intermediates. Wor. J. Pharm. Res, 2014, 3, 2111-2126.
[74]
Hanif, M.; Hussain, M.; Ali, S.; Bhatti, M.H.; Ahmed, M.S.; Mirza, B.; Evans, H.S. Synthesis, spectroscopic investigation, crystal structure, and biological screening, including antitumor activity of organotin(IV) derivatives of piper- onylic acid. Turk. J. Chem., 2007, 31, 349-361.
[75]
Bushra, I.; Kanwal, J.; Muhammad, S.; Ullah, K.; Zareen, A.; Bushra, M.; Vickie, M. Synthesis, characterization and biological assay of Salicylaldehyde Schiff base Cu(II) complexes and their precursors. J. Mol. Struct., 2018, 1155, 337-348.
[76]
Tripathi, L.; Kumar, P.; Singhal, A.K. Role of chelates in treatment of cancer. Indian J. Cancer, 2007, 44, 62-71.
[77]
Hellen, F.G.B.; Maha, A.; Ana, P.G.F.; Edward, R.D.; Nour, E.E.; Bruno, M.M.; Éder Tadeu, G.C. Synthesis, characterization and biological activities of biopolymeric schiff bases prepared with chitosan and salicylaldehydes and their Pd(II) and Pt(II) complexes. Molecules, 2017, 22(11), 12.
[78]
Kavitha, P.; Laxma, R.K. Synthesis, spectral characterisation, morphology, biological activity and DNA cleavage studies of metal complexes with chromone Schiff base. Arab. J. Chem., 2016, 9, 596-605.
[79]
Quiroga, A.G.; Pérez, J.M.; López-Solera, I.; Masaguer, J.R.; Luque, A.; Román, P.; Edwards, A.; Alonso, C.; Navarro-Ranninger, C. Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA. J. Med. Chem., 1998, 41, 1399-1408.

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