Research Article
The synthesis and evaluation of anti-acetylcholinesterase activity of some 4(3H)-quinazolinone derivatives bearing substituted 1,3,4- thiadiazole
Abstract
In the present study, a series of 4(3H)-quinazolinone derivatives (5a-f) were synthesized through the cylization reaction of substituted 1,3,4-thiadiazoles containing an aromatic primary amin and anthranilic acid in the presence of acetic anhydride and acetic acid. The structures of the synthesized compounds were confirmed by elemental analysis (C,H,N,S), IR, 1H-NMR and mass spectroscopic (5b and 5f) methods. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modification of Ellman’s spectrophotometric method. Compounds 2-methyl-3-{4-[5-(ethylamino)-1,3,4-thiadiazol-2-yl]phenyl}quinazolin-4(3H)-one (5b) and 2-methyl-3-{4-[5-(cyclohexylamino)-1,3,4-thiadiazol-2-yl]phenyl}quinazolin-4(3H)-one (5d) can be identified as promising anticholinesterase agents due to their inhibitory effect when compared with Donepezil (IC50 =0.054±0.002 μM) as a reference drug.
References
- World Alzheimer Report 2015. The Global Impact of Dementia. An analysis of prevalence, incidence, cost and trends. Available at; https://www.alz.co.uk/research/world-report-2015.
- Auriacombe S, Pere JJ, Loria-Kanza Y, Vellas B. Efficacy and Safety of Rivastigmine in Patients with Alzheimer's Disease who Failed to Benefit from Treatment with Donepezil. Curr Med Res Opin 2002; 18: 129-38.
- Skrzypek A, Matysiak J, Karpińska MM, Niewiadomy A. Synthesis and anticholinesterase activities of novel 1,3,4-thiadiazole based compounds. J Enzyme Inhib Med Chem 2013; 28: 816-23.
- Altıntop MD, Kaplancıklı ZA, Özdemir A, Turan-Zitouni G, Temel HE, Akalın G. Synthesis and Anticholinesterase Activity and Cytotoxicity of Novel Amide Derivatives. Archiv der Pharmazie 2012; 345: 112-6.
- Cao SL, Feng YP, Jiang YY, Liu SY, Ding GY, Li RT. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bioorg Med Chem Lett 2005; 15: 1915-7.
- Noolvi MN , Patel HM, Bhardwaj V, Chauhan A. Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: Search for anticancer agent. Eur J Med Chem 2011; 46: 2327-46.
- Chatterjee N, Das S, Bose D, Banerjee S, Das S, Chattopadhyay D, Saha KD. Exploring the anti-inflammatory activity of a novel 2-phenylquinazoline analog with protection against inflammatory injury. Toxicol Appl Pharmacol 2012; 264: 182-91.
- Desai NC, Bhat JJ, Shah BR, Undavia NK, Trivedi PB, Narayanan V. Synthesis of substituted quinazolone derivatives as potential anti-hiv agents (part III). Farmaco 1996; 51: 361-6.
- Fischer C, Shah S, Hughes BL, Nikov GN, Crispino JL, Middleton RE, Szewczak AA, Munoz B, Shearman MS. Quinazolinones as γ-secretase modulators. Bioorg Med Chem Lett 2011; 21: 773-6.
- Decker M. Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids dehydroevodiamine and rutaecarpine. Eur J Med Chem 2005; 40: 305-13.
- Li Z, Wang B, Hou JQ, Huang SL, Ou TM, Tan JH, An LK, Li D, Gu LQ, Huang ZS. 2-(2-Indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling. J Enzyme Inhib Med Chem 2013; 28: 583-92.
- Darras FH, Wehle S, Huang G, Sotriffer CA, Decker M. Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with ‘inverted’ binding mode. Bioorg Med Chem 2014; 22: 4867-81.
- Jagania CL, Vanparia SF, Patel TS, Dixit RB, Dixit BC. A comparative study of solution phase as well as solvent free microwave assisted syntheses of 3-benzothiazole/isoxazole substituted 2-styryl-4(3H)-quinazolinones. ARKIVOC 2012; (vi): 281-94.
- Karima I, Baya B, Fariza C, Cherifa R, Maâmar H, Safouane MH. A Microwave-Assisted and Heteropolyacids-Catalysed Cyclocondensation Reaction for the Synthesis of 4(3H)-Quinazolinones. Molecules 2008; 13: 779-89.
- Abdel-Jalil RJ, Voelter W, Saeed M. A novel method fort he synthesis of 4(3H)-quinazolines.Tetrahedron Lett 2004; 45: 3475-6.
- Khan I, Ibrar A, Ahmed W, Saeed A. Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: The advances continue. Eur J Med Chem 2015; 90: 124-69.
- Karakuş S, Rollas S. Synthesis and antimycobacterial activity of some 2-(4-amino-phenyl)-5-substitutedamino-1,3,4-thiadiazole derivatives and their coupling products. Marmara Pharm J 2016; 20: 199-206.
- Karalı N, İlhan E, Gürsoy A, Kiraz M. New cyclohexylidenehydrazide and 4-aza-1-thiaspiro[4.5]decan-3-one derivatives of 3-phenyl-4(3H)-quinazolinones. Farmaco 1998; 53: 346-9.
- Khalil MA, Habib NS. Synthesis of thiadiazolo derivatives of 4(3H)-quinazolinone as potential antimicrobial agents. Farmaco 1987; 43: 973-8.
- Patel NB, Patel JC. Synthesis and antimicrobial activity of 3-(1,3,4-oxadiazol-2-yl)quinazolin-4(3H)-ones. Sci Pharm 2010; 78: 171–93.
- Jatav V, Mishra P, Kashaw S, Stables JP. Synthesis and CNS depresassant activity of some novel 3-[5-substituted-1,3,4-thiadiazole-2-yl]-2-styrylquinazoline-4(3H)-ones. Eur J Med Chem 2008; 43: 135-41.
- Bhat AR, Shenoy GG, Kotlan M. Synthesis and biological activities of mannich bases of 7-nitro-2-methyl-4(3H)-quinazolinone. Indian J Heterocycl Chem 2000; 9: 319-20.
- Perry NSL, Houghton PJ, Theobald A, Jenner P, Perry EK. In-vitro Inhibition of Human Erythrocyte Acetylcholinesterase by Salvia lavandulaefolia Essential Oil and Constituent Terpenes. J Pharm Pharmacol 2000; 52: 895-902.
- Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88-90.
1,3,4-Tiyadiazol içeren bazı 4(3H)-kinazolinon türevlerinin sentezi ve anti-asetilkolinesteraz aktiviteleri
Abstract
Bu çalışmada, aromatik pirimer
amin içeren sübstitüe 1,3,4-tiyadiazoller
ile antranilik asitin asetik asit ve asetik
anhidritli ortamdaki siklizasyonundan bir seri 4(3H)- kinazolinon türevi (5a-f) sentez edildi.
Bileşiklerin yapıları IR, 1H-NMR, kütle
spektroskopisi (5b ve 5f) ve elementel analiz
yöntemleri kullanılarak aydınlatıldı. Bileşiklerin aktivite tayini Ellman’ın modifiye edilmiş
spektrofotometrik yöntemi kullanılarak
yapıldı. Donepezil standardı ile karşılaştırıldığında bileşik 5b (2-metil-3-{4-[5-(etilamino)-1,3,4-tiyadiazol-2-il] fenil}kinazolin-4(3H)-on) ve bileşik 5d
(2-metil-3-{4-[5- (siklohegzilamino)-1,3,4-tiyadiazol-2-il]fenil}kinazolin-4(3H)- on) inhibitör etkilerine göre
antikolinesteraz ajanları olarak tanımlanabilirler.
References
- World Alzheimer Report 2015. The Global Impact of Dementia. An analysis of prevalence, incidence, cost and trends. Available at; https://www.alz.co.uk/research/world-report-2015.
- Auriacombe S, Pere JJ, Loria-Kanza Y, Vellas B. Efficacy and Safety of Rivastigmine in Patients with Alzheimer's Disease who Failed to Benefit from Treatment with Donepezil. Curr Med Res Opin 2002; 18: 129-38.
- Skrzypek A, Matysiak J, Karpińska MM, Niewiadomy A. Synthesis and anticholinesterase activities of novel 1,3,4-thiadiazole based compounds. J Enzyme Inhib Med Chem 2013; 28: 816-23.
- Altıntop MD, Kaplancıklı ZA, Özdemir A, Turan-Zitouni G, Temel HE, Akalın G. Synthesis and Anticholinesterase Activity and Cytotoxicity of Novel Amide Derivatives. Archiv der Pharmazie 2012; 345: 112-6.
- Cao SL, Feng YP, Jiang YY, Liu SY, Ding GY, Li RT. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bioorg Med Chem Lett 2005; 15: 1915-7.
- Noolvi MN , Patel HM, Bhardwaj V, Chauhan A. Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: Search for anticancer agent. Eur J Med Chem 2011; 46: 2327-46.
- Chatterjee N, Das S, Bose D, Banerjee S, Das S, Chattopadhyay D, Saha KD. Exploring the anti-inflammatory activity of a novel 2-phenylquinazoline analog with protection against inflammatory injury. Toxicol Appl Pharmacol 2012; 264: 182-91.
- Desai NC, Bhat JJ, Shah BR, Undavia NK, Trivedi PB, Narayanan V. Synthesis of substituted quinazolone derivatives as potential anti-hiv agents (part III). Farmaco 1996; 51: 361-6.
- Fischer C, Shah S, Hughes BL, Nikov GN, Crispino JL, Middleton RE, Szewczak AA, Munoz B, Shearman MS. Quinazolinones as γ-secretase modulators. Bioorg Med Chem Lett 2011; 21: 773-6.
- Decker M. Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids dehydroevodiamine and rutaecarpine. Eur J Med Chem 2005; 40: 305-13.
- Li Z, Wang B, Hou JQ, Huang SL, Ou TM, Tan JH, An LK, Li D, Gu LQ, Huang ZS. 2-(2-Indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling. J Enzyme Inhib Med Chem 2013; 28: 583-92.
- Darras FH, Wehle S, Huang G, Sotriffer CA, Decker M. Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with ‘inverted’ binding mode. Bioorg Med Chem 2014; 22: 4867-81.
- Jagania CL, Vanparia SF, Patel TS, Dixit RB, Dixit BC. A comparative study of solution phase as well as solvent free microwave assisted syntheses of 3-benzothiazole/isoxazole substituted 2-styryl-4(3H)-quinazolinones. ARKIVOC 2012; (vi): 281-94.
- Karima I, Baya B, Fariza C, Cherifa R, Maâmar H, Safouane MH. A Microwave-Assisted and Heteropolyacids-Catalysed Cyclocondensation Reaction for the Synthesis of 4(3H)-Quinazolinones. Molecules 2008; 13: 779-89.
- Abdel-Jalil RJ, Voelter W, Saeed M. A novel method fort he synthesis of 4(3H)-quinazolines.Tetrahedron Lett 2004; 45: 3475-6.
- Khan I, Ibrar A, Ahmed W, Saeed A. Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: The advances continue. Eur J Med Chem 2015; 90: 124-69.
- Karakuş S, Rollas S. Synthesis and antimycobacterial activity of some 2-(4-amino-phenyl)-5-substitutedamino-1,3,4-thiadiazole derivatives and their coupling products. Marmara Pharm J 2016; 20: 199-206.
- Karalı N, İlhan E, Gürsoy A, Kiraz M. New cyclohexylidenehydrazide and 4-aza-1-thiaspiro[4.5]decan-3-one derivatives of 3-phenyl-4(3H)-quinazolinones. Farmaco 1998; 53: 346-9.
- Khalil MA, Habib NS. Synthesis of thiadiazolo derivatives of 4(3H)-quinazolinone as potential antimicrobial agents. Farmaco 1987; 43: 973-8.
- Patel NB, Patel JC. Synthesis and antimicrobial activity of 3-(1,3,4-oxadiazol-2-yl)quinazolin-4(3H)-ones. Sci Pharm 2010; 78: 171–93.
- Jatav V, Mishra P, Kashaw S, Stables JP. Synthesis and CNS depresassant activity of some novel 3-[5-substituted-1,3,4-thiadiazole-2-yl]-2-styrylquinazoline-4(3H)-ones. Eur J Med Chem 2008; 43: 135-41.
- Bhat AR, Shenoy GG, Kotlan M. Synthesis and biological activities of mannich bases of 7-nitro-2-methyl-4(3H)-quinazolinone. Indian J Heterocycl Chem 2000; 9: 319-20.
- Perry NSL, Houghton PJ, Theobald A, Jenner P, Perry EK. In-vitro Inhibition of Human Erythrocyte Acetylcholinesterase by Salvia lavandulaefolia Essential Oil and Constituent Terpenes. J Pharm Pharmacol 2000; 52: 895-902.
- Ellman GL, Courtney KD, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88-90.
There are 24 citations in total.
Details
| Subjects | Health Care Administration |
|---|---|
| Journal Section | Articles |
| Authors | |
| Publication Date | September 9, 2016 |
| Published in Issue | Year 2017 Volume: 21 Issue: 1 |