Synthesis and pharmacological evaluation of some quinoline derivatives as potential cognition enhancers

Abstract

The present paper describes the synthesis of a series of substituted 6-amino (1 a–c) and 8-aminoquinoline derivatives (2b–c) and the evaluation of their ability to prevent the memory decline using a behavioural model, i. e. the elevated plus maze test. The effect of the candidate drugs on the activity of acetylcholinesterase was studied using the enzyme source from the mouse brain. The structures of the synthesized compounds were confirmed by UV, IR, ¹H-NMR and elemental analysis. The 6-aminoquinoline derivative [6-(4-pyridyl)methylaminoquinoline] (1 c) oxalate showed maximum % retention (50% at 5 mg/kg and 75% at 10 mg/kg) in the elevated plus maze test and maximum% inhibition (71% at 25 µM) of AChE on biochemical evaluation.

Key words

Acetycholinesterase - 6-Aminoquinolines - 8-Aminoquinolines - Cogniton enhancers - Elevated plus maze - Quinolines

• References

• 1 Marta M, Castellano C, Oliverio A, Pavone F, Pagella PG, Brufani M et al. New analogues of physostigmine: alternative drugs for Alzheimer’s disease?. Life Sci. 1988; 43: 1921-8
• 2 Gualtieri F. Cholinergic receptors and neurodegenerative diseases. Pharm Acta Helv. 2000; 74: 85-9
• 3 Benzi G, Moretti A. Is there a rationale for the use of acetylcholinesterase inhibitors in the therapy of Alzheimer’s disease?. Eur J Pharmacol. 1998; 346: 1-13
• 4 Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A. Oral tetrahydroaminoacridine in long term treatment of senile dementia, Alzheimer type. N Engl J Med. 1986; 315: 1241-5
• 5 Bartus RT, Dean RL, Beer B, Lippa AS. The cholinergic hypothesis for geriatric memory disfunction. Science 1982; 217: 408-14
• 6 Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, Thomas DJ et al. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem. 1983; 40: 503-9
• 7 Gottfries CG. Pharmacological treatment strategies in Alzheimer’s type dementia. Psychopharmacology 1985; 86: 245-4
• 8 Perry EK. The cholinergic hypothesis-ten years on. Br Med Bull. 1986; 40: 503-9
• 9 Barril X, Kalko SG, Orozco M, Luque FJ. Rational design of reversible acetylcholinesterase inhibitors. Mini Rev Med Chem. 2002; 2: 27-36
• 10 Recanatini M, Cavalli A, Belluti F, Piazzi L, Rampa A, Bisi A et al. SAR of 9-amino-l,2,3,4-tetrahydroacridine based acetylcholinesterase inhibitors: Synthesis, enzyme inhibitory activity, QSAR and structure-based COMFA of tacrine analogues. J Med Chem. 2000; 43: 2007-18
• 11 Camps P, Achab RE, Morral J, Munoz-Torrero D, Badia A, Banos JE et al. New tacrine-hyperzine A hybrids (huprines): Highly potent tight-binding acetylcholinesterase inhibitors of interest for the treatment of Alzheimer’s disease. J Med Chem. 2000; 43: 4657-66
• 12 Camps P, Achab RE, Gorbig DM, Morral J, Munoz-Tarrero D, Badia A et al. Synthesis in vitro pharmacology and molecular modeling of very potent tacrine-hyperzine A hybrids as acetylcholinesterase inhibitors of Alzheimer’s disease. J Med Chem. 1999; 42: 3227-42
• 13 Suzuki T, Usui T, Oka M, Suzuki T, Kataoka T. Synthesis and muscarinic activity of a series of quinolines and naphthalenes with a l-azabicyclo[3.3.0]octane moiety. Chem Pharm Bull. 1998; 46: 1265-73
• 14 Piplani P, Rani A, Sandhir R, Kulkarni SK. Synthesis and pharmacological evaluation of some quinoline derivatives as potential antiamnesic agents. J Young Pharmacists. 2009; 1: 341-50
• 15 Vetulani J, Battaglia M, Sansone M. Nimodipine on shuttle box avoidance Learning in mice: no improvement but slight impairment. Pharmacol Biochem Behav. 1996; 56: 577-81
• 16 Halama A, Kavalek J, Machacek V, Weidlich T. Aromatic nucleophilic subsititution of hydrogen: Mechanism of reaction of 6-nitroquinoline with cyanide ions, with and without participation of methyl cyanoacetate. J Chem Soc Perkin Trans. 1999; 1: 1839-45
• 17 Sharma AC, Kulkarni SK. Evaluation of learning and memory mechanisms employing elevated plus maze in rats and mice. Prog Neuropsychopharmacol Biol Psychiat. 1992; 16: 117-25
• 18 Ellman GL, Courtney KD, Andress V, Featherston RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7: 88-95
• 19 Lowry OH, Rosenberg NJ, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951; 193: 265-2
• 20 Baker RH, Albisetti CJ, Dodson RM, Lappin GR, Riegel B. The synthesis of some 8-aminoquinolines. J Am Chem Soc. 1946; 68: 1532-6
• 21 Furniss BS, Hannaford AJ, Smith PWG, Tatchell AR. Vogel’s textbook of practical organic chemistry. 5th ed. New York: John Wiley & Sons; 1989. p. 890-92