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Isoxazole compounds: Unveiling the synthetic strategy, in-silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy.

Authors :
Malik U
Pal D
Source :
European journal of medicinal chemistry [Eur J Med Chem] 2024 Dec 05; Vol. 279, pp. 116898. Date of Electronic Publication: 2024 Sep 24.
Publication Year :
2024

Abstract

Latest developments in cancer treatment have shed a light on the crucial role of PARP inhibitors that enhance the treatment effectiveness by modifying abnormal repair pathways. PARP inhibitors, such as Olaparib, Rucaparib, Niraparib, and Talazoparib have been approved in a number of cancers including BRCA 1/BRCA2 associated malignancies although there are many difficulties as therapeutical resistance. Besides the conventional synthetic drugs, natural compounds such as flavones and flavonoids have been found to be PARP inhibitors but only in preclinical studies. Isoxazole is very important class of potential candidates for medicinal chemistry with anti-cancer and other pharmacological activities. At present, there are no approved PARP inhibitors of isoxazole origin but their ability to hit many pathways inside the cancer cells points out on its importance for future treatments design. In drug development, isoxazoles are helpful because of the molecular design flexibility that may be enhanced using various synthetic approaches. This review highlights the molecular mechanisms of PARP inhibition, importance of isoxazole compounds and present advances in their synthetic strategies that demonstrate promise for these agents as new anticancer drugs. It emphasizes that isoxazole-based PARP inhibitors compounds could be novel anti-cancer drugs. Through this review, we hope to grow a curiosity in additional explorations of isoxazole-based PARP inhibitors and their applications in the trends of novel insights towards precision cancer therapy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Details

Language :
English
ISSN :
1768-3254
Volume :
279
Database :
MEDLINE
Journal :
European journal of medicinal chemistry
Publication Type :
Academic Journal
Accession number :
39353240
Full Text :
https://doi.org/10.1016/j.ejmech.2024.116898