Design, synthesis, 99mTc labeling, and biological evaluation of a novel pyrrolizine derivative as potential anti-inflammatory agent

被引：12
作者：
Attallah K.M. [1 ,2 ]
Gouda A.M. [3 ,4 ]
Ibrahim I.T. [2 ]
Abouzeid L. [5 ]
机构：
[1] Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah
[2] Labeled Compounds Department, Hot Laboratories Center, Atomic Energy Authority, P.O. Box 13759, Cairo
[3] Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef
[4] Department of Pharmaceutical Chemistry, College of Pharmacy, Umm Al-Qura University, Makkah
[5] Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura
来源：
Radiochemistry | 2017年 / 59卷 / 6期
关键词：
anti-inflammatory drugs; COX; infection; inflammation; pyrrolizine; technetium-99m;
D O I：
10.1134/S10663622170600121
中图分类号：
学科分类号：
摘要：
The design and synthesis of ethyl 4-(6-amino-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamido)-benzoate (KH16) were discussed, and its structure was determined. The anti-inflammatory activity of a new compound was evaluated using in vitro cyclooxygenase (COX) inhibitory assay. KH16 exhibits higher selectivity to COX-2 than to COX-1 with the selectivity index of 3.46. KH16 was labeled with 99mTc with the maximum radiochemical yield of 99mTc-KH16 of 90.5 ± 1.5%. Biodistribution of 99mTc-KH16 in normal, infected, and inflamed mice was studied. The uptake in inflamed muscle was higher than that in normal muscle throughout the examined time interval. This work is a step ahead in the direction of using pyrrolizine derivatives for site-specific delivery to the inflamed tissue. © 2017, Pleiades Publishing, Inc.
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页码：630 / 638
页数：8
相关论文
共 38 条
[1]  
Roberts L.J., Morrow J.D., The Pharmacological Basis of Therapeutics, pp. 687-733, (2001)
[2]  
Schneider V., Levesque L.E., Zhang B., Et al., Am. J. Epidemiol., 164, pp. 881-889, (2006)
[3]  
Cryer B., Am. J. Gastroenterol., 100, pp. 1694-1695, (2005)
[4]  
Singh G., Am. J. Med., 105, pp. 31S-38S, (1998)
[5]  
Vane J.R., Botting R.M., Scand. J. Rheumatol. Suppl., 102, pp. 9-21, (1996)
[6]  
Smith C.J., Zhang Y., Koboldt C.M., Et al., Proc. Nat. Acad. Sci., 95, pp. 133-138, (1998)
[7]  
Sarkar F.H., Adsule S., Li Y., Padhye S., Mini Rev. Med. Chem., 7, pp. 599-608, (2007)
[8]  
Gouda A.M., Abdelazeem A.H., Eur. J. Med. Chem., 114, pp. 257-292, (2016)
[9]  
Laufer S.A., Augustin J., Dannhardt G., Kiefer W., J. Med. Chem., 37, pp. 1894-1897, (1994)
[10]  
Bias P., Buchner A., Klesser B., Laufer S., Am. J. Gastroenterol., 99, pp. 611-618, (2004)
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