Development of New Potential Anticancer Metal Complexes Derived from 2-Hydrazinobenzothiazole

Page: [913 - 922] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: Due to the side effects of clinically approved anticancer drugs there is a great need to explore and develop new metal-based anticancer drug molecules of high efficiency with less or no side effects.

Objective: To synthesize new metal complexes of 2-hydrazinobenzothiazole (hbt) and to investigate their potential anticancer characteristics.

Methods: New five complexes; [VO(hbt)2SO4].4H2O (1), [Ru(hbt)2Cl3(H2O)] (2), [M(hbt)2Cl2] [M(II) = Pd (3), Pt (4)] and [Ag(hbt)2].NO3 (5) were prepared and their structure was investigated by means of FTIR, 1H NMR, ESI-MS and UV-Vis spectra, elemental and thermal analysis, magnetic and molar conductance measurements. The ligand and its complexes were examined as anticancer agents against Ehrlich ascites carcinoma (EAC) and human cancer cells (hepatocellular carcinoma Hep-G2, mammary gland breast cancer MCF-7 and colorectal carcinoma HCT-116). This feature is further supported by the DNAmetal complexes binding ability. In addition, anti-oxidation activity of the complexes was investigated.

Results: Complex (5) shows the highest anticancer activity with IC50 of 5.15, 9.9, 13.1 and 17.7 µg/mL for EAC, HePG-2, MCF-7 and HCT-116, respectively. Complexes (2) and (3) show promising cytotoxicity against EAC and HePG-2 cells with IC50 5.49 and 16.2 µg/mL, respectively. While, complexes (1) and (4) show optimistic cytotoxicity against EAC with IC50 of 9.63 and 11.25 µg/mL, respectively. The order of DNA binding ability of the complexes is (5) > (3) > (2) > (1) > (4). Among the five complexes, complex (5) shows the best anti-oxidation activity.

Conclusion: Complex (5) showed the highest DNA binding ability, anti-oxidation and anticancer activities.

Keywords: Anticancer, antioxidant, cytotoxic, DNA, palladium, silver, spectra.

Graphical Abstract

[1]
Saad, E.A.; Habib, S.A.; Eltabeey, M. Diagnostic performance of afp, autotoxin and collagen iv and their combinations for non-invasive assessment of hepatic fibrosis staging in liver fibrosis patients associated with chronic HCV. IJPQA, 2017, 8(4), 165-173.
[http://dx.doi.org/10.25258/ijpqa.v8i04.10542]
[2]
Saad, E.A.; Hassanien, M.M.; Elneely, E.A. Iron(III) diacetylmonoxime-2-hydrazinopyridine complex: A new prospective antitumor drug. Appl. Organomet. Chem., 2017, 31(9)e3684
[http://dx.doi.org/10.1002/ aoc.3684]
[3]
Saad, E.A.; Hassanien, M.M.; El-lban, F.W. Nickel (II) diacetyl monoxime-2-pyridyl hydrazone complex can inhibit Ehrlich solid tumor growth in mice: A potential new antitumor drug. Biochem. Biophys. Res. Commun., 2017, 484(3), 579-585.
[4]
Saad, E.A.; Hassanien, M.M.; El-Mezayen, H.A.; Elmenawy, N.M. Regression of murine ehrlich ascites carcinoma using synthesized cobalt complex. MedChemComm, 2017, 8, 1103-1111.
[http://dx.doi.org/10.1039/C6MD00618C]
[5]
Hadaji, E.G.; Ouammou, A.; Bouachrine, M. QSAR study of anthra[ 1,9-cd]pyrazol-6(2H)-one derivatives as potential anticancer agents using statistical methods. Adv. Chem, 2018, 2018Article ID 3121802, 16 pages..
[http://dx.doi.org/10.1155/2018/3121802.]
[6]
Bakthadoss, M.; Mushaf, M. A distal vinyl shift (DVS) through quadruple dominoreaction: synthesis of N-vinyl benzoheterocyclic scaffolds. RSCAdv., 2018, 8, 12152.
[http://dx.doi.org/10.1039/c8ra01478g]
[7]
Prakash, P.; Ganpat, L.T. New benzothiazole-thiazolidinone hybrids containing phthalimidoxy and ethoxyphthalimide: design, synthesis and pharmacological assay. Organic & Medicinal Chem. IJ., 2018, 5(4)555673
[http://dx.doi.org/10.19080/OMCIJ.2018.05.555673]
[8]
Mathis, C.A.; Wang, Y.; Holt, D.P.; Huang, G-F.; Debnath, M.L.; Klunk, W.E. Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J. Med. Chem., 2003, 46, 2740-2754.
[9]
Prajapati, N.P.; Vekariya, R.H.; Borad, M.A.; Patel, H.D. Recent advances in the synthesis of 2-substituted benzothiazoles: A review. RSC Advances, 2014, 4, 60176-60208.
[10]
Keri, R.S.; Patil, M.R.; Patil, S.A.; Budagumpi, S. A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem., 2015, 89, 207-251.
[11]
Nalawade, A.; Nalawade, M.R.; Patange, M.S.; Tase, M.D.; Badawy, A.; Omer, A.; Saksena, D.P.; Demaki, G.; Anyaegbunam, F.; Allahdadi, H. Thiazole containing schiffs bases and their transition metal complexes. IJESI, 2013, 1, 1-4.
[12]
Shabana, A.A.; Butler, I.S.; Gilson, D.F.; Jean-Claude, B.J.; Mouhri, Z.S.; Mostafa, M.M.; Mostafa, S.I. Synthesis, characterization, anticancer activity and DNA interaction studies of new 2-aminobenzothiazole complexes; Crystal structure and DFT calculations of [Ag(Habt)2]ClO4. Inorg. Chim. Acta, 2014, 423, 242-255.
[13]
El-Asmy, H.A.; Butler, I.S.; Mouhri, Z.S.; Jean-Claude, B.J.; Emmam, M.; Mostafa, S.I. Synthesis, characterization and DNA interaction studies of new complexes containing 2-mercaptobenzothiazole and different dinitrogen or phosphorous aromatic donors. Inorg. Chim. Acta, 2016, 441, 20-33.
[14]
McLimans, W.F.; Davis, E.V.; Glover, F.L.; Rake, G.W. The submerged culture of mammalian cells: The spinner culture. J. Immunol., 1957, 79, 428-433.
[15]
Mauceri, H.J.; Hanna, N.N.; Beckett, M.A.; Gorski, D.H.; Staba, M-J.; Stellato, K.A.; Bigelow, K.; Heimann, R.; Gately, S.; Dhanabal, M. Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature, 1998, 394, 287-291.
[16]
Burres, N.S.; Frigo, A.; Rasmussen, R.R.; McAlpine, J.B. A colorimetric microassay for the detection of agents that interact with DNA. J. Nat. Prod., 1992, 55, 1582-1587.
[17]
Morimoto, Y.; Tanaka, K.; Iwakiri, Y.; Tokuhiro, S.; Fukushima, S.; Takeuchi, Y. Protective effects of some neutral amino acids against hypotonic hemolysis. Biol. Pharm. Bull., 1995, 18, 1417-1422.
[18]
Lissi, E.A.; Modak, B.; Torres, R.; Escobar, J.; Urzua, A. Total antioxidant potential of resinous exudates from Heliotrapium species, and a comparison of the ABTS and DPPH methods. Free Radic. Res., 1999, 30, 471-477.
[19]
Bhagat, T.; Swamy, D.; Deshpande, M. Synthesis and characterization of transition metal complexes with newly synthesized substituted benzothiazole. J. Chem. Pharm. Res., 2012, 4, 100-104.
[20]
Aboafia, S.A.; Elsayed, S.A.; El-Sayed, A.K.A.; El-Hendawy, A.M. New transition metal complexes of 2,4-dihydroxybenzaldehyde benzoylhydrazone schiff base (H2dhbh): Synthesis, spectroscopic characterization, DNA binding/cleavage and antioxidant activity. J. Mol. Struct., 2018, 1158, 39-50.
[http://dx.doi.org/10.1016/ j.molstruc.2018.01.008]
[21]
Thangadurai, T.D.; Ihm, S-K. Tetradentate schiff base ruthenium (II) carbonyl complexes: Synthesis, characterisation, catalytic and antibacterial studies. JIEC, 2003, 9(5), 569-575.
[22]
Dodoff, N.; Grancharov, K.; Spassovska, N. Platinum (II) complexes of 4-methoxy-and 4-chlorobenzoic acid hydrazides. Synthesis, characterization, and cytotoxic effect. J. Inorg. Biochem., 1995, 60, 257-266.
[23]
Lakshmi, P.A.; Reddy, P.S.; Raju, V.J. Synthesis, characterization and antimicrobial activity of 3d transition metal complexes of a biambidentate ligand containing quinoxaline moiety. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc., 2009, 74, 52-57.
[24]
Nakamoto, K. Infrared and Raman spectra of inorganic and coordination compounds; Hoboken Wiley Online Library, 1986.
[25]
Elsayed, S.A.; Butler, I.S.; Claude, B.J.; Mostafa, S.I. Synthesis, characterization and anticancer activity of 3-formylchromone benzoylhydrazone metal complexes. Transit. Metal Chem., 2015, 40, 179-187.
[26]
Nakamoto; K.; Nakamoto, K. Infrared and Raman spectra of inorganic and coordination compounds; Hoboken: Wiley, 1977.
[27]
Kadirova, S.A.; Tursunova, M.; Ishankhodzhaeva, M.; Parpiev, N.; Karimov, Z.; Tozhiboev, A.; Tashkhodzhaev, B. Synthesis and structure of complexes of Co (II) acetate and Zn (II) chloride with 2-aminobenzothiazole. Russ. J. Gen. Chem., 2007, 77, 1807-1810.
[28]
Elsayed, S.A.; El-Hendawy, A.M.; Mostafa, S.I.; Butler, I.S. Transition metal complexes of 2-formylpyridinethiosemicarbazone (HFpyTSC) and X-Ray crystal structures of [Pd (FpyTSC)(PPh3)] PF6 and.[Pd (FpyTSC)(SCN)]. Inorganica. Chim. Acta, 2010, 363, 2526-2532.
[29]
Mostafa, S.I.; Hadjiliadis, N. Biologically active 2-thione-4, 6-diamino-5-hydroxypyrimidine transition metal complexes. Transit. Metal Chem., 2008, 33, 529-534.
[30]
Ghosh, T.; Bhattacharya, S.; Das, A.; Mukherjee, G.; Drew, M.G. Synthesis, structure and solution chemistry of mixed-ligand oxovanadium (IV) and oxovanadium (V) complexes incorporating tridentate ONO donor hydrazone ligands. Inorg. Chim. Acta, 2005, 358, 989-996.
[31]
Taqui Khan, M.; Srinivas, D.; Kureshy, R.; Khan, N. Synthesis, characterization, and EPR studies of stable ruthenium (III) schiff base chloro and carbonyl complexes. Inorg. Chem., 1990, 29, 2320-2326.
[32]
Ouf, A.E-F.; Ali, M.S.; Saad, E.M.; Mostafa, S.I. pH-metric and spectroscopic properties of new 4-hydroxysalicylidene-2-aminopyrimidine schiff-base transition metal complexes. J. Mol. Struct., 2010, 973, 69-75.
[33]
Mostafa, S.I.; Perlepes, S.P.; Hadjiliadis, N. New dinuclear transition metal complexes with the [M2 (μ-dhbq)] n+ core and 2-(2′-Pyridyl) quinoxaline (L) as a terminal ligand: preparation and characterization (dhbq2-= the Dianion of 2, 5-Dihydroxy-1, 4-benzoquinone; M= AgI, MnII, CoII, NiII, CuII, RuII, PdII, FeIII, RhIII; n= 0, 2, 4). Zeitschrift für. Naturforsch. B, 2001, 56, 394-402.
[34]
Özpozan, N.; Arslan, H.; Özpozan, T.; Özdeş, N.; Külcü, N. Thermal studies of Ni (II), Pd (II), Pt (II) and Ru (III) complexes of N, N-dihexyl-N′-benzoylthiourea. Thermochim. Acta, 2000, 343, 127-133.
[35]
Mostafa, S.I. Mixed ligand complexes with 2-piperidine-carboxylic acid as primary ligand and ethylene diamine, 2, 2′-bipyridyl, 1, 10-phenanthroline and 2 (2′-pyridyl) quinoxaline as secondary ligands: Preparation, characterization and biological activity. Transit. Metal Chem., 2007, 32, 769-775.
[36]
Elsayed, S.A.; El-Hendawy, A.M.; Mostafa, S.I.; Jean-Claude, B.J.; Todorova, M.; Butler, I.S. Antineoplastic activity of new transition metal complexes of 6-methylpyridine-2-carbaldehyde-n (4)-ethylthiosemicarbazone: X-Ray crystal structures of [VO2(mpETSC)] and [Pt (mpETSC) Cl]. Bioinorg. Chem. Appl., 2010, 2010149149
[37]
Ibrahim, F.M.; El-Hawary, Y.M.; Butler, I.S.; Mostafa, S.I. Bone repair stimulation in rat mandible by new chitosan silver (i) complexes. Int. J. Polym. Mater. Po., 2014, 63, 846-858.
[38]
Kostova, I. Platinum complexes as anticancer agents. Recent Patents Anticancer Drug Discov., 2006, 1, 1-22.
[39]
Bazzicalupi, C.; Biagini, S.; Bianchi, A.; Biver, T.; Boggioni, A.; Giorgi, C.; Gratteri, P.; Malavolti, M.; Secco, F.; Valtancoli, B. DNA interaction with Ru (II) and Ru (II)/Cu (II) complexes containing azamacrocycle and dppz residues. A thermodynamic, kinetic and theoretical study. Dalton Trans., 2010, 39, 9838-9850.
[40]
Brabec, V.; Nováková, O. DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity. Drug Resist. Updat., 2006, 9, 111-122.
[41]
Novotny, L.; Kombian, S.B. Vanadium: Possible use in cancer chemoprevention and therapy. J. Cancer Res. Updates, 2014, 3, 97-102.
[42]
Chang, Y-M.; Chen, C.K-M.; Hou, M-H. Conformational changes in DNA upon ligand binding monitored by circular dichroism. Int. J. Mol. Sci., 2012, 13, 3394-3413.
[43]
Frik, M.; Fernández-Gallardo, J.; Gonzalo, O.; Mangas-Sanjuan, V.; González-Alvarez, M.; del Valle, A.S.; Hu, C.; González-Alvarez, I.; Bermejo, M.; Marzo, I. Cyclometalated iminophosphorane gold (III) and platinum (II) complexes. A highly permeable cationic platinum (II) compound with promising anticancer properties. J. Med. Chem., 2015, 58, 5825.
[44]
Frik, M.; Jiménez, J.; Vasilevski, V.; Carreira, M.; de Almeida, A.; Gascón, E.; Benoit, F.; Sanaú, M.; Casini, A.; Contel, M. Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents. Inorg. Chem. Front., 2014, 1, 231-241.
[45]
Gao, E-J.; Wang, K-H.; Zhu, M-C.; Liu, L. Hairpin-shaped tetranuclear palladium (II) complex: synthesis, crystal structure, DNA binding and cytotoxicity activity studies. Eur. J. Med. Chem., 2010, 45, 2784-2790.
[46]
Habib, S.A.; Saad, E.A.; Elsharkawy, A.A.; Attia, Z.R. Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents. Adv. Med. Sci., 2015, 60, 179-185.
[47]
Saad, E.A. Curative and protective effects of L-arginine on carbon tetrachloride-induced hepatotoxicity in mice. Biochem. Biophys. Res. Commun., 2012, 423, 147-151.
[48]
Saad, E.A.; Habib, S.A. Effect of crude extracts of some medicinal plants on the osmotic stability of human erythrocytes in vitro. J. Free Rad. Antiox. Photon, 2013, 139, 265-272.
[49]
Saad, E.A. Kidney response to L-arginine treatment of carbon tetrachloride-induced hepatic injury in mice. Nat. Sci., 2013, 5(1), 1-6.
[http://dx.doi.org/10.4236/ns.2013.51001]
[50]
Sun, Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic. Biol. Med., 1990, 8, 583-599.
[51]
Saad, E.A.; Hassanien, M.M.; El-Hagrasy, M.A.; Radwan, K.H. Antidiabetic, hypolipidemic and antioxidant activities and protective effects of Punica granatum peels powder against pancreatic and hepatic tissues injuries in streptozotocin induced iddm in rats. Int. J. Pharm. Pharm. Sci., 2015, 7, 397-402.
[52]
Saad, E.A.; Toson, E.A.; Ahmed, G.M. Clove or green tea administration antagonizes khat hepatotoxicity in rats. Int. J. Pharm. Pharm. Sci., 2015, 7(6), 72-76.
[53]
Saad, E.A. Non-invasive assessment of liver fibrosis using serum markers. J. Pharm. Chem. Biol. Sci, 2014, 2(2), 59-76.