Synthesis and characterization of pyrimidines analogues as anti-Alzheimer’s agents

doi:10.5246/jcps.2017.11.094

Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (11): 834-846.DOI: 10.5246/jcps.2017.11.094

• Original articles • Previous Articles Next Articles

Synthesis and characterization of pyrimidines analogues as anti-Alzheimer’s agents

Yadav Rakesh^*, Maan Monika, Yadav Divya

Department of Pharmacy, Banasthali University, Banasthali-304022 Rajasthan, India

Received:2017-05-17 Revised:2017-06-19 Online:2017-11-30 Published:2017-09-28
Contact: Tel.: +91-96-948-91228, E-mail: rakesh_pu@yahoo.co.in

Abstract

Abstract:

Pyrimidine derivatives have been reported as neuroprotective agents useful for the treatment of various neurodegenerativedisorders. In the present study, several pyrimidine analogues have been evaluated as neuroprotective agents in Morris water maze model. It was observed that pyrimidine derivatives 8–17 considerably improve learning, memory, and movement deficits in animal models. Biochemical estimations of brain serum of treated animals revealed suppression of oxidative and nitrosative stress, acetylcholinesterase activity, and other parameters which leads to neurodegeneration of brain. Of all the pyrimidine derivatives, thiomorpholine derivative 8 and piperazine ethanol derivative 17 were found to be the most active neuroprotective agents and produced effects comparable to standard drug rivastigmine in terms of behavioral, biochemical, and molecular aspects.

Key words: Alzheimer’s disease, Neurodegeneration, Pyrimidine derivatives, Biochemical tests

CLC Number:

R916

Supporting:

Yadav Rakesh, Maan Monika, Yadav Divya. Synthesis and characterization of pyrimidines analogues as anti-Alzheimer’s agents[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(11): 834-846.

References

[1] Mohamed, T.; Roa, P.P.N. Bioorg. Med. Chem. Lett. 2010, 20, 3606-3609.

[2] Thies, W.; Bleiler, L. Alzheimer’s Dementia. 2011, 7, 208-244.

[3] Pakaski, M.; Kalman, J. Neurochem. Int. 2008, 53, 103-111.

[4] Tabet, N. Age. Ageing. 2006, 35, 336-338.

[5] Shen, T.; Tai, K.; Henchman, R.H.; Mccammon, J.A. Accounts. Chem. Res. 2002, 35, 332-340.

[6] Matysiak, J.; Nasulewicz, A.; Pelcznska, M.; Switalska, M.; Jaroszewicz, A. Eur. J. Med. Chem. 2006, 41, 475-482.

[7] Mohamed, T.; Zhao, X.; Habib, L.K.; Yang, J.; Rao, P.P.N. Bioorg. Med. Chem. 2011, 19, 2269-2281.

[8] Darvesh, S.; Pottie, I.R.; Darvesh, K.V.; McDonald, R.S.; Walsh, R.; Conard, S.; Penwell, A.; Mataija, D.; Martin, E. Bioorg. Med. Chem. 2010, 18, 2232-2244.

[9] Morris, R.G.M.; Garrud, P.; Rawlins, J.N.P.; O’Keefe, J. Nature. 1982, 297, 681-683.

[10] Ellman, G.L.; Courtney, K.D.; Andres, V.; Featherstone, R.M. Biochem. Pharmacol. 1961, 7, 88-95.

[11] Misra, S.; Tiwari, V.; Kuhad, A.; Chopra, K. Eur. J. Pharmacol. 2011, 659, 177-186.

[12] Bansal, N.; Parle, M. J. Med. Food. 2010, 13, 1293-1300.

[13] Bano, T.; Kumar, N.; Dudhe, R. Chem. Cent. J. 2012, 2, 1-6.

[14] Pachauri, S.D.; Tota, S.; Khandelwal, K.; Verma, P.R.P.; Nath, C.; Hanif, K.; Dwivedi, A. K. J. Ethnopharmacol. 2012, 139, 34-41.

[15] El-Sherbiny, D.A.; Khalifa, A.E.; Attia, A.S.; Eldenshary, E.D. Pharmacol. Biochem .Behav. 2003, 76, 525-533.

[16] Smith, D.G.; Cappai, R.; Barnham, K.J. Biochim. Biophys. Acta. Biomembr. 2007, 1768, 1976-1990.

[17] Kanwal, A.; Mehla, J.; Kuncha, M.; Naidu, V.G.M.; Gupta, Y.K.; Sistla, R. Pharmacol. Pharm. 2010, 1, 1-8.

[18] Abu-Hashem, A.A.; Youssef, M.M.; Hoda, A.R. J. Chin. Chem. Soc. 2011, 58, 41-48.

[19] Wills, E.D. Biochem. J. 1966, 99, 667-676.

[20] Jollow, D.J.; Mitchell, J.R.; Zampaglione, N.; Gillette, J.R. Pharmacology. 1974, 11, 151-169.

[21] Dhingra, D.; Parle, M.; Kulkarni, S.K. Indian. J. Pharm. Sci. 2004, 66, 371-376.

[22] Schmeller, T.; Sporer, F.; Sauerwein, M.; Wink, M. Pharmazie. 1995, 50, 493-495.

[23] Sharma, A.; Parikh, V.; Singh, M. Indian. J. Exp. Biol. 1997, 35, 1146-1155.

Synthesis and characterization of pyrimidines analogues as anti-Alzheimer’s agents

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 7

Recommended Articles

Metrics

Comments

[1]	Peng Lv, Can Li, Yan Niu, Hongyue Li, Tongliang Zhou, Fengrong Xu, Lei Liang, Chao Wang, Ping Xu. Design, synthesis, and in vitro activity of methylisoxazole/isothiazole amides as BACE1 inhibitors [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(3): 143-158.
[2]	Jiapei Yu, Yan Niu, Qi Sun, Fengrong Xu, Lei Liang, Chao Wang, Ping Xu. Design and synthesis of 2-aminobenzimidazoles as potential BACE1 inhibitors [J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(9): 650-659.
[3]	Shasha Ji, Yun Lei, Xiaotian Huang, Zhiqin Gao. Protective effects of β-dihydroagarofuran-type sesquiterpene against Aβ25-35-induced neuronal apoptosis and oxidative damage [J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(8): 582-589.
[4]	Lidan Bai, Xue Li, Qing Chang, Rui Wu, Jing Zhang, Xiaoda Yang. Cinnamaldehyde promotes mitochondrial function and reduces Aβ toxicity in neural cells [J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(8): 605-613.
[5]	Xue Li, Lidan Bai, Yaqiong Dong, Qing Chang, Rui Wu, Jing Zhang, Xiaoda Yang. Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the βamyloid burden in SHSY5Y neural cells [J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(10): 754-763.
[6]	Xin Zhao, Shiping Zhang, Chunna An, Hongning Zhang, Yi Sun, Yanmei Li, Xiaoping Pu. Neuroprotective effect of fucoxanthin on β-amyloid-induced cell death [J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(7): 467-474.
[7]	Ying Hu, Yanfang Yang, Wenzhi Yang, Yingtao Zhang. In vitro studies on the multi-target anti-Alzheimer activities of berberine-like alkaloids from Coptidis Rhizoma [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(6): 385-392.