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

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Radiochemistry Aims and scope

Abstract

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.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    K. M. Attallah

  2. Labeled Compounds Department, Hot Laboratories Center, Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt

    K. M. Attallah & I. T. Ibrahim

  3. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt

    A. M. Gouda

  4. Department of Pharmaceutical Chemistry, College of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    A. M. Gouda

  5. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt

    L. Abouzeid

Authors
  1. K. M. Attallah
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  2. A. M. Gouda
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  3. I. T. Ibrahim
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  4. L. Abouzeid
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Correspondence to K. M. Attallah.

Additional information

Published in Russian in Radiokhimiya, 2017, Vol. 59, No. 6, pp. 554–561.

The text was submitted by the authors in English.

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Attallah, K.M., Gouda, A.M., Ibrahim, I.T. et al. Design, synthesis, 99mTc labeling, and biological evaluation of a novel pyrrolizine derivative as potential anti-inflammatory agent. Radiochemistry 59, 630–638 (2017). https://doi.org/10.1134/S10663622170600121

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  • DOI: https://doi.org/10.1134/S10663622170600121

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