Synthesis and acetylcholinesterase (AChE) inhibitory activity of some N-substituted-5-chloro-2(3H)- benzoxazolone derivatives

Year 2013, Volume: 17 Issue: 1, 15 - 20, 07.03.2014

Zeynep Soyer Sulunay Parlar Vildan Alptuzun

Abstract

ABSTRACT: Alzheimer’s disease is a progressive neurodegenerative disorder of the central
nervous system. Acetylcholinesterase inhibition is one of the proposed mechanisms for
treatment of Alzheimer’s disease. Currently, acetylcholinesterase inhibitors such as tacrine,
donepezil, rivastigmine and galantamine are applied in different stages of Alzheimer’s disease
teratment. In recent years, various heterocyclic systems have been used as a skeleton
to discover new acetylcholinesterase inhibitors. On the other hand, it is known that the benzoxazolone
heterocyclic structure exhibited a wide range of biological activities. In this
study, a series N-substituted-5-chloro-2(3H)-benzoxazolone derivatives were synthesized
and evaluated their acetylcholinesterase inhibitory activity. These compounds were synthesized
by Mannich reaction of 5-chloro-2(3H)-benzoxazolone with the appropriated amines.
The acetylcholinesterase inhibitory activity of the title compounds was determined by colorimetric
Ellman’s method. The preliminary screening results indicated that 5-chloro-2-(3H)-
benzoxazolone scaffold demonstrated different inhibition range against acetylcholinesterase
enzyme depending on the structural differences.
KEY WORDS: acetylcholinesterase Inhibitory activity, 2(3H)-benzoxazolone, mannich reaction,
Ellman’s method, synthesis.

Keywords

acetylcholinesterase Inhibitory activity, 2(3H)-benzoxazolone, mannich reaction, Ellman’s method, synthesis.

Synthesis and acetylcholinesterase (AChE) inhibitory activity of some N-substituted-5-chloro-2(3H)- benzoxazolone derivatives

Abstract

References

• Andreani A, Cavalli A, Granaiola M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Recanatini M, Roda A. Synthesis and screening for anticholinesterase activity of (1-benzyl4-oxopiperidin-3-ylidine) methylindoles and pyrroles related to Donepezil. J Med Chem 2006; 44: 4011-4.
• Viegas C, Bolzani VS, Pimentel LSB, Castro NG, Cabral RF, Costa RS, Floyd C, Rocha MS, Young MCM, Barreiro EJ, Fraga CA. New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids. Bioorg Med Chem 2005; 13: 4184-90.
• Ladner CJ, Lee JM. Pharmacological drug treatment of Alzheimer disease: the cholinergic hypothesis revisited. J Neuropathol Exp Neurol 1998; 57: 719-31.
• De Ferrari GV, Canales MA, Shin I, Weiner LM, Silman I, Inestrosa NC. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry 2001; 40: 10447-57.
• Racchi, M, Azzucchelli MA, Porrello E, Lanni C, Govoni S. Acetylcholinesterase inhibitors: Novel activities of old molecules. Phamacol Res 2004; 50: 441-51.
• Wilkinson, D. Pharmacotherapy of Alzheimer’s disease. Psychiatry 2008; 7: 9-14.
• Williams, BR, Nazarians A, Gill MA. A review of rivastigmine: A reversible cholinesterase inhibitor. Clin Ther 2003; 25: 1634-8.
• Ago Y, Koda K, Takuma K and Matsuda T. Pharmacological Aspects of the Acetylcholinesterase Inhibitor Galantamine. J Pharmacol Sci 2011; 116: 6-17.
• Deng BL, Cullen MD, Zhou Z, Hartman TL, Buckheit RW Jr, Pannecouque C, Clercq ED, Fanwick PE, Cushman M. Synthesis and anti-HIV activity of new alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors (NNRTIs) incorporating benzoxazolone and benzisoxazole rings. Bioorg Med Chem 2006; 14: 2366-74.
• Ivanova Y, Momekov G, Petrov O, Karaivanova M, Kalcheva V. Cytotoxic Mannich bases of 6-(3-aryl2-propenoyl)-2(3H)-benzoxazolones. Eur J Med Chem 2007; 42: 1382-7.
• Unlu S, Onkol T, Dundar Y, Okcelik B, Kupeli E, Yesilada E, Noyanalpan N, Sahin MF. Synthesis, analgesic and anti-inflammatory activity of some new 6-acyl2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid residues. Arch Pharm 2003; 336: 353-61.
• Koksal M, Gokhan N, Kupeli E, Yesilada E, Erdogan H. Synthesis, Analgesic and Antiinflammatory Properties of certain 5-/6-Acyl-3-(4-substituted-1-piperazinylmethyl)2-benzoxazolinone derivatives. Arch Pharm 2005; 338: 117Onkol T, Ito S, Yildirim E, Erol K, Sahin MF. Synthesis and Antinociceptive Activity of (2-Benzazolon-3-yl)propionamide Derivatives. Arch Pharm 2001; 334: 17-20.
• Koksal M, Gokhan N, Erdogan H, Ozalp M, Ekizoglu M. Synthesıs of 3-(4-substituted benzoylmethyl)-2-benzoxazolinones and screening antimicrobial activities. Il Farmaco 2002; 57: 535-8.
• Ucar H, Van derpoorten K, Cacciaguerra S, Spampinato, Stables JP, Depovere P, Isa M, Masereel B, Delarge J, Poupaert JH. Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives. J Med Chem 1998; 41: 1138-45.
• Courtois M, Mincheva Z, Andreu F, Rideau M, ViaudMassuard MC. Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ring. J Enzyme Inhib Med Chem 2004; 19: 559-65.
• Soyer Z, Baş M, Pabuçcuoğlu A, Pabuçcuoğlu V. Synthesis of some 2(3H)-benzoxazolone derivatives and their in-vitro effects on human leukocyte myeloperoxidase activity. Arch Pharm 2005; 338: 405-10.
• Swahn BM, Wensbo D, Sandell J, Sohn D, Slivo C, Pyring D, Malmström J, Arzel E, Vallin M, Bergh M, Jeppsson F, Allan E. Johnson, Juréus A, Neelissen J, Svensson S. Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for β-amyloid plaques. Bioorg Med Chem Lett 2010; 20: 1976-80.
• Refolo LM, Fillit, HM. Drug discovery for Alzheimer’s disease: the end of beginning. J Mol Neurosci 2004; 24: 1-8.
• Nachman RJ. Convenient preparation of 2-benzoxazolinones with 1,1-carbonyldiimidazole. J Heterocycl Chem 1982; 19: 1545-7.
• Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88-95.
• Kapkova P, Stiefl N, Sürig U, Engels B, Baumann K, Holzgrabe U. Synthesis, Biological Activity and Docking Studies of New Acetylcholinesterase Inhibitors of the Bispyridinium Type. Arch Pharm 2003; 336: 523-40.
• Aydın A, Soyer Z, Akkurt M and Büyükgüngör O. 3-Anilinomethyl-5-chloro-1,3- benzoxazol-2(3H)-one. Acta Cryst 2012; 68: 1544-5.
• Varma RS, Nobles WL. Synthesis and antibacterial activity of certain 3-substituted benzoxazolinone. J Pharm Sci 1968; 57: 39-44.
• Kalcheva V, Godisnik na Sofiiskiya Universitet Sv. Kliment Okhridski, Khimicheski Fakultet, 1971, Volume Date 1968-1969; 63: 375-83.
• Hesse M, Meier H, Zeeh B. Spectroscopic Methods in Organic Chemistry. Stuttgart, New York. 1997.
• Nakanishi K, Solomon PH. Infrared Absorption Spectroscopy Emerson Adams Press Inc, San Francisco. 1977.