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Vol. 38 No. 6 (2026): Vol. 38 Issue No 6, 2026

Copyright (c) 2026 Subhash Chander, Karan Goel, Katarzyna Wanke, Mateusz Kciuk, Renata Kontek, Thakur Gurjeet Singh, Somdutt Mujwar

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This work is licensed under a Creative Commons Attribution 4.0 International License.

Computational Design, Synthesis and Biological Evaluation of Some Novel 1H-Pyrrolizine Carboxylic Acid Derivatives as Anticancer Agents

https://doi.org/10.14233/ajchem.2026.35929
Subhash Chander
Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India; Research and Development Department, Valence Lab, Jansui Village, Rajpura-140401, India
https://orcid.org/0009-0004-4478-6102
Karan Goel
Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India
https://orcid.org/0009-0006-3367-613X
Katarzyna Wanke
Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland; Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
https://orcid.org/0009-0000-9010-8493
Mateusz Kciuk
Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland
https://orcid.org/0000-0002-8616-3825
Renata Kontek
Department of Molecular Biotechnology and Genetics, University of Lodz, 90-237 Lodz, Poland
https://orcid.org/0000-0003-2859-9839
Thakur Gurjeet Singh
Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India
https://orcid.org/0000-0003-2979-1590
Somdutt Mujwar
Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India
https://orcid.org/0000-0003-4037-5475

Corresponding Author(s) : Somdutt Mujwar

somduttmujwar@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 6 (2026): Vol. 38 Issue No 6, 2026

Abstract

Licofelone is a 1H-pyrrolizine carboxylic acid based dual COX/5-LOX inhibitor, emerges as a promising therapeutic candidate due to its ability to simultaneous interference of both inflammatory pathways, but its clinical translation is restricted by its poor pharmacokinetics. The current research aims to design novel 1H-pyrrolizine carboxylic acid derivatives with the intent to improve the pharmacokinetics and explore their anticancer potential. The docking analysis of the designed analogues showed potent binding with COX-2, 5-LOX and some other anticancer targets, especially indoleamine 2,3-dioxygenase-1 (IDO1), in comparison with parent molecule. A synthetic procedure was developed and optimised for the synthesis of designed compounds followed by assessing their anticancer potential by performing an MTT assay. The obtained results have concluded that the designed licofelone-derived pyrrolizine analogues revealed that structural modifications with different amino acid conjugates significantly influenced their anticancer activity with compound 8b and 8c exhibited the most potent antiproliferative activity against PANC-1 cells with IC50 values of 1.7 ± 0.2 µM and 1.4 ± 0.05 µM, respectively. These molecules can be further used to develop novel anticancer therapeutics post preclinical and clinical validation.

Keywords

Licofelone Anticancer activity Docking studies MTT assay COX/5-LOX inhibitor 1H-Pyrrolizine carboxylic acid
(1)
Chander, S.; Goel, K.; Wanke, K.; Kciuk, M.; Kontek, R.; Singh, T. G.; Mujwar, S. Computational Design, Synthesis and Biological Evaluation of Some Novel 1H-Pyrrolizine Carboxylic Acid Derivatives As Anticancer Agents. ajc 2026, 38, 1652-1662.
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