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Open Access Review

Pyrrolizines: natural and synthetic derivatives with diverse biological activities

by Samir M. El-Moghazy Aly 1 ,  Mohamed A. Azim Mohamed 1 ,  Ahmed M. Shawky 2 ,  Faisal A. Almalki 3 ,  Ashraf N. Abdalla 4,5 ,  Bahaa G.M. Youssif 6 ,  Ahmed H. Abdelazeem 7,8 ,  Nashwa, A. Ibrahim 7  and  Ahmed M. Gouda 7,* orcid
1
Pharmaceutical Chemistry Department Faculty of Pharmacy, Cairo University Cairo, Egypt.
2
Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia
3
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
4
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
5
Department of Pharmacology and Toxicology, Medicinal And Aromatic Plants Research Institute, National Center for Research, Khartoum 2404, Sudan.
6
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
7
Medicinal chemistry department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
8
Pharmacy Department, College of pharmacy, Nursing and Medical Sciences, Riyadh Elm University, Riyadh 11681, Saudi Arabia.
*
Author to whom correspondence should be addressed.
IJCMR  2024 2(5):38; https://doi.org/10.61466/ijcmr2050003
Received: 9 July 2024 / Accepted: 13 September 2024 / Published Online: 17 September 2024
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Abstract

The pyrrolizine nucleus is a bicyclic ring system that consists of a pyrrole ring fused to another pyrrolidin ring. It constitutes the basic skeleton in many natural and synthetic compounds with diverse biological activities such as the anti-inflammatory, nootropic, antiemetic, antibacterial, antiviral, anticonvulsant, antiarrhythmic, and anticancer activities. At least two of these derivatives, ketorolac and mitomycin C, have been approved for the treatment of inflammation and cancer, respectively. Licofelone, a dual inhibitor of COX and 5-LOX, was also evaluated in clinical trials for the treatment of osteoarthritis. On the other hand, a large number of the pyrrolizine-based derivatives have displayed anticancer activity against different types of cancer cells. In this review, the pyrrolizine-based derivatives with anticancer activity were classified based on their chemical structure into substituted, fused, and spiro-pyrrolizine. The mechanisms of action of these compounds included alkylation of the DNA, inhibition of COX, or alteration of the permeability of the cytoplasmic membrane in cancer cells. In addition, other pyrrolizines were found to act by inhibiting DNA replication, rRNA, Rac1 kinase, thioredoxin reductase, or oncogenic kinases. The last section of this review also focuses on the reported X-ray crystal structures of these compounds with different proteins. The binding modes and interactions of ketorolac and licofelone were illustrated in this review. To sum up, we anticipate that the data compiled in this review will be useful to researchers in the design of pyrrolizines with potent biological activities.

Keywords: pyrrolizine; mechanism of action; anticancer; anti-inflammatory, binding interactions;
Copyright: © 2024 by Aly, Mohamed, Shawky, Almalki, Abdalla, Youssif, Abdelazeem, Ibrahim and Gouda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (Creative Commons Attribution 4.0 International License). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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ACS Style
Aly, S. M. E.; Mohamed, M. A. A.; Shawky, A. M.; Almalki, F. A.; Abdalla, A. N.; Youssif, B. G.; Abdelazeem, A. H.; Ibrahim, N. A.; Gouda, A. M. Pyrrolizines: natural and synthetic derivatives with diverse biological activities. International Journal of Clinical Medical Research, 2024, 2, 38. https://doi.org/10.61466/ijcmr2050003
AMA Style
Aly S M E, Mohamed M A A, Shawky A M, Almalki F A, Abdalla A N, Youssif B G, Abdelazeem A H, Ibrahim N A, Gouda A M. Pyrrolizines: natural and synthetic derivatives with diverse biological activities. International Journal of Clinical Medical Research; 2024, 2(5):38. https://doi.org/10.61466/ijcmr2050003
Chicago/Turabian Style
Aly, Samir M. E.; Mohamed, Mohamed A. A.; Shawky, Ahmed M.; Almalki, Faisal A.; Abdalla, Ashraf N.; Youssif, Bahaa G.; Abdelazeem, Ahmed H.; Ibrahim, Nashwa, A.; Gouda, Ahmed M. 2024. "Pyrrolizines: natural and synthetic derivatives with diverse biological activities" International Journal of Clinical Medical Research 2, no.5:38. https://doi.org/10.61466/ijcmr2050003
APA style
Aly, S. M. E., Mohamed, M. A. A., Shawky, A. M., Almalki, F. A., Abdalla, A. N., Youssif, B. G., Abdelazeem, A. H., Ibrahim, N. A., & Gouda, A. M. (2024). Pyrrolizines: natural and synthetic derivatives with diverse biological activities. International Journal of Clinical Medical Research, 2(5), 38. https://doi.org/10.61466/ijcmr2050003

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