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Coumarin or benzoxazinone bearing benzimidazolium and bis(benzimidazolium) salts; involvement in transfer hydrogenation of acetophenone derivatives and hCA inhibition

Mert Olgun Karataş, Serkan Dayan, Nilgün Kayacı, Çiğdem Bilen, Emre Yavuz, Nahit Gencer, Bülent Alıcı, Nilgün Ozpozan Kalaycıoğlu, Oktay Arslan

Abstract


Four new salts of benzimidazolium and bis(benzimidazolium) which include coumarin or benzoxazinone moieties were synthesized and the structures of the newly synthesized compounds were elucidated on the basis of spectral analyses such as 1H-NMR, 13C-NMR, HSQC, IR, LC-MS and elemental analysis. Benzimidazolium salts were used intensively as N-heterocyclic carbene (NHC) precursors in the various catalytic reactions such as transfer hydrogenation (TH), C-H bond activation, Heck, Suzuki reaction etc. With the prospect of potential NHC precursor properties of the synthesized compounds, they were employed in the (TH) reaction of p-substitute acetophenones (acetophenone, p-methyl acetophenone, p-chloro acetophenone) and good yields were observed. Coumarin compounds are known as inhibitor of carbonic anhydrase and inhibition effects of the synthesized compounds on human carbonic anhydrases (hCA) were investigated as in vitro. The in vitro results demonstrated that all compounds inhibited hCA I and hCA II activity. Among the synthesized compounds 1,4-bis(1-((6,8-dimethyl-2H-chromen-2-one-4-yl)methyl)benzimidazolium-3-yl)butane dichloride was found to be the most active IC50= 5.55 mM and 6.06 mM for hCA I and hCA II, respectively.

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H.A. Barker, R.D. Smyth, H. Weissbach, J.I. Toohey and B.E. Volcani, Isolation and properties of crystalline cobamide coenzymes containing benzimidazole or 5,6-dimethylbenzimidazole, J. Biol. Chem., 1960, 235, 480-488.

Keiji Kubo et al., Nonpetide angitensin II receptor antagonists. Synthesis and biological activity of benzimidazoles, J. Med. Chem., 1993, 36, 1772-1784.

K.C.S. Achar, K.M. Hosamani and H.R. Seethaaramareddy, In-vivo analgesic and anti-inflammatıry of newly synthesized benzimidazole derivatives, Eur. J. Med. Chem., 2010, 45, 2048-2054.

K.G. Desai and K.R. Desai, Green route for the heterocyclization of 2-mercaptobenzimidazole into -lactum segment derivatives containing –CONH- bridge with benzimidazole: Screening in vitro antimicrobial activity with various microorganisms, Bioorg. Med. Chem., 2006, 14, 8271-8279.

Svetlana K. Kotouskaya et al. ,Synthesis and antiviral activity of fluorinated pyrido[1,2-a]benzimidazles, Pharm. Chem. J., 2005, 39, 574-578.

E.R. Cole, G. Crank and Salam-Sheikh, Antioxidant properties of benzimidazoles, J. Agr. Food Chem., 1974, 22, 918.

H.M. Refaat, Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives, Eur. J. Med. Chem., 2010, 45, 2949-2956.

Jeremy M. Travins et al., 1-(3-aryloxaryl)benzimidazole sulfones are liver X receptor agonists, Bioorg. Med. Chem. Lett., 2010, 20, 526-530.

Norbert H. Hauel et al., Structure based design of novel potent nonpeptide thrombin inhibitors, J. Med. Chem., 2002, 45, 1757-1766.

S. Cekirdek, S. Yasar and I. Ozdemir, Palladium (II)-N-heterocyclic carbene complexes: synthesis, characterization and catalytic application, Appl. Organomet. Chem., 2014, 28, 423-431.

S. Demir, M. Yigit and I. Ozdemir, Synthesis of rhodium complexes derived from benzimidazolin-2-yliden ligands and first used for the addition of arylboran to benzonitriles, J. Organomet. Chem., 2013, 732, 21-26.

Dharmendra Kumar et al., Cationic iron(II) complexes of the mixed cyclopentadienyl(cp) and the N-heterocyclic carbine (NHC) ligands as effective precatalysts for the hydrosilyation of carbonyl compounds, J. Organomet. Chem., 2014, 762, 81-87.

H. Turkmen, S. Denizaltı and I. Ozdemir, E. Cetinkaya, B. Cetinkaya, Synthesis and use of mono or bisxylyl linked bis(benzimidazolium) bromides as carbene precursurs for C-C bond formation reactions, J. Organomet. Chem., 2008, 693, 425-434.

N. Gurbuz, S. Demir, I. Ozdemir, B., New 1,2,4,5-tetrakis-(N-imidazoliniummethyl)benzene and 1,2,4,5-tetrakis(N-benzimidazoliniummethyl)benzene salts as N-heterocyclic tetracarbene precursors; synthesis and involvement in ruthenium catalyzed allylation reactions, Cetinkaya and C. Bruneau, Tetrahedron, 2010, 66, 1346-1351.

A. Slamani, S. Demir and I. Ozdemir, Use of benzimidazolium salts for in situ generation of palladium catalysts in Heck reactions in water, Catal. Commun., 2012, 29, 141-144.

R. Noyori and S. Hashiguchi, Asymmetric transfer hydrogenation catalyzed by chiral ruthenium complexes, Acc. of Chem. Res., 1997, 30, 97-102.

I. Yamada and R. Noyori, Asymmetric transfer hydrogenation of benzaldehydes, Org. Lett., 2000, 2, 3425-3427.

S. Dayan, F. Arslan and N.K. Ozpozan, Ru(II) impregnated Al2O3, Fe3O4, SiO2, and N-coordinate ruthenium (II) arene complexes: Multifunctional catalysts in the hydrogenation of nitroarenes and the transfer hydrogenation of aryl ketones, Appl. Catal. B:Environmental, 2015, 164, 305-315.

G.S. Clark, Coumarin: An aroma chemical profile, Perfumer and Flavonist, 1995, 20, 23-24.

B.G. Lake, Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment, Food and Chem Toxic., 1997, 37, 423-453.

P. Anand, B. Singh and M. Singh, A review on coumarins as acetylcholinesterase inhibitors for Alzheimer’s disease, Bioorg. Med. Chem., 2012, 20, 1175-1180.

D. Yu, M. Suzuki, L. Xie, S.L. Morris-Natschke and K.H. Lee, Recent progress in the development of coumarin derivatives as potent anti-HIV agents, Med. Res. Rev., 2003, 23, 322-345.

Alfonso Maresca et al., Non-zinc mediated inhibition of carbonic anhydrases: Coumarins are a new class of suicide inhibitors, J. Am. Chem. Soc., 2009, 131, 3057-3062.

Alfonso Maresca et al., Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocomarins, J. Med. Chem., 2010, 53, 335-344.

M.G. Nair, D.C. Salter, R.L. Kisliuk, Y. Gaumont and G. North, Folate analogs.22.Synthesis and biological evaluation of two analogs of dihydro folic acid possesing a 7,8-dihydro-8-oxapterin ring system, J. Med. Chem., 1983, 26, 1164-1168.

Y. Katsura, S. Nishino and H. Takasugi, Studies on antiulcer drugs. I.Synthesis and antiulcer activities of imidazo[1,2-alpha]pyrdnyl-2-oxobenzoxazolidines-3-oxo-2H-1,4-benzoxazines and related compounds, Chem. Pharm. Bull., 1991, 39, 2937-2943.

M. Kajino, Y. Shibouta, K. Nishikawa and K. Megura, Synthesis and biological activities of new 2-substitute 1,4-benzoxazine derivatives, Chem. Pharm. Bull., 1991, 38, 2896-2905.

S. Wahidulla and J.J. Bhattaeharje, Benzoxazinoids from Acanthus illicifolius, J. Indian Inst. Sci., 2001, 81, 485-490.

Liang Fang et al., Synthesis of benzo[b][1,4] oxazin-3(4H)-ons via smiles rearrengement for antimicrobial activity, Med. Chem. Res., 2011, 20, 670-677.

Xiaokai Li et al., Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agent against Mycobacterim tuberculosis, Bioorg. Med. Chem. Lett., 2010, 20, 6306-6309.

R. Fringuelli, N. Giacche, L. Milanese, E. Cenci and F. Macchiarulo, Bulky 1,4-benzoxazine derivatives with antifungal activity, Bioorg. Med. Chem., 2009, 17, 3838-3846.

C.F. Turk, J. Krapcho, I.M. Miche and I. Weinryb, Synthesis and central nervous system activity of 2-aryliden-4-aminoalkyl-2H-1,4-benzoxazen-3(4H)-ones and related compounds, J. Med. Chem., 1997, 20, 730-732.

A. Thiry, J.M. Dogne, C.T. Supuran and B. Masareel, Carbonic anhydrase inhibitors of anticonvulsant agents, Curr. Top Med. Chem., 2007, 7, 855-864.

C.T. Supuran, Carbonic anhydrases: Novel therapeutic application for inhibitors and activators, Nat. Rev. Drug Discov., 2008, 7, 168-181.

A. Thiry, J.M. Dagne, B. Masareel and C.T. Supuran, Targeting tumor-associated carbonic anhydrase IX in cancer therapy, Trends Pharmacol. Sci., 2006, 27, 566-573.

James M. McKiernan et al., Expression of the tumor-associated gene MN: A potential biomarker for human renal cell carcinoma, Cancer. Res., 1997, 57, 2362-2365.

A. Scozzafava, A. Mastrolorenzo and C.T. Supuran, Carbonic anhydrase inhibitors and activator and their use in therapy, Expert Opin. Ther. Pat., 2006, 16, 1627-1664.

C.T. Supuran, A. Scozzafava and A. Casini, Carbonic anhydrase inhibitors, Med. Res. Rev., 2003, 23, 146-189.

K.S. Smith and J.G. Ferry, Prokaryotic carbonic anhydrases, FEMS Microbial Rev., 2000, 24, 335-366.

T. Stams and D.W. Christianson, X-ray crystallographic studies of mammalian carbonic anhydrase isozymes. In: Chegwidden WR, Carter ND, Edwards YH, eds. X-ray crystallographic studies of mammalian carbonic anhydrase isozymes. The Carbonic Anhydrases: New Horizons. Boston: Birkhauser Verlag, 2000, 159-174.

S. Pastorekova, S. Parkilla, J. Pastorek and C.T. Supuran, Carbonic anhydrases: Current state of art, therapeutic applications and future prospects, J. Enzyme Inhib. Med. Chem., 2004, 19, 199-229.

Isao Nishimori et al., Carbonic anhydrase inhibitors: Claning, characterization and inhibiton studies of the cytosolic isoenzyme III with sulphonamides, Bioorg. Med. Chem., 2007, 15, 7229-7236.

D. Vullo, M. Franchi, E. Gallori, A. Scozzafava and C.T. Supuran, Carbonic anhydrase inhibitors.Inhibiton of mitochondrial isoenzyme V with aromatic and heterocyclic sulphonamides, J. Med. Chem., 2004, 47, 1272-1279.

Isao Nishimori et al., Carbonic anhydrase inhibitors. The mithocondrial isoenzyme VB as a new target for sulfonamide and sulfomate inhibitors, J. Med. Chem., 2005, 48, 7860-7866.

Isao Nishimori et al., Carbonic anhydrase inhibitors. DNA claning, characterization and inhibiton studies of human secretary isoform VI, a new targer for sulfonamide and sulfomate inhibitors, J. Med. Chem., 2007, 50, 381-388.

Daniela Vullo et al., Carbonic anhydrase inhibitors. Inhibition of the human cytosolic isoenzyme VII with aromatic and heterocyclic sulphonamides, Bioorg. Med. Chem. Lett., 2005, 15, 971-976.

Daniela Vullo et al., Carbonic Anhydrase inhibitors. Inhibiton of transmembrane isoenzyme XII with sulfonamides- a new target for design of antitumor and antigloucoma drugs?, Bioorg. Med. Chem. Lett., 2005, 15, 963-969.

M.S. Frasinyuk, V.I. Vinogradova, S.P. Bondarenko and V.P. Khilya, Synthesis of cytosine derivatives of coumarins, Chem. Nat. Comp., 2007, 43, 176-180.

I. Ozdemir, N. Sahin, S. Demir and B. Cetinkaya, In situ generated 1-alkylbenzimidazoles-palladium catalyst for the Suzuki coupling of aryl chlorides, J. Molec. Catal. A, 2005, 234, 181-185.

O. Arslan, B. Nalbantoglu, N. Demir, H. Ozdemir and O.I. Kufrevioglu, A new method for the purification of carbonic anhydrase izoenzymes by affinity chromatography, Turk. J. Med. Sci., 1996, 26, 163-166.

T.H. Maren, A simplified micromethod for the determination of carbonic anhydrase and its inhibitors J. Pharm. Exp. Ther., 1960, 130, 2629-2634.


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