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Volume 21, Issue 17
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Cancer represents the major health problem faced by the population of the world, remaining one of the main causes of death. Hence, the development of new targeted antitumor drugs with high efficacy and lower toxicity is still needed.

Objective

As a continuation of our work to discover new molecules with cytotoxic properties, two heterocyclic scaffolds, namely indolizine, and indazole, were combined in the same molecule, aiming to improve the bioactivity. This article focused on the synthesis, characterization, and biological evaluation of a series of new indazole-indolizine hybrid compounds.

Methods

The biological potential of the synthesized compounds was investigated against the human farnesyltransferase enzyme and NCI 60 tumor cell lines panel. While the farnesyltransferase inhibitory activity was modest, a very good antiproliferative action was observed for compound , which, at a concentration of 10 µM, inhibited the growth of 20 types of cancer cells by more than 50% and showed cytotoxic action against the ovarian cancer cell line OVCAR-4.

Results

A series of novel indazole-indolizine hybrids were synthesized a [3+2] cycloaddition reaction, fully characterized and biologically evaluated for antitumor potential.

Conclusion

Compound could be a promising starting point in the development of new antitumoral agents. Further biological investigations will be performed to identify the biological target of the compounds. Moreover, different synthetic strategies to introduce new substituents on the indolizine core will be addressed.

© 2024 Bentham Science Publishers
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2024-10-21
2025-04-13

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Exploring the Antitumor Potential of New Indazole-indolizines Designed by Molecular Hybridization
Letters in Drug Design & Discovery 21, 4046 (2024); https://doi.org/10.2174/0115701808323543241018053705
/content/journals/lddd/10.2174/0115701808323543241018053705
/content/journals/lddd/10.2174/0115701808323543241018053705
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  • Article Type:     Research Article
Keyword(s): [3+2] cycloaddition; farnesyltransferase; hybrid molecule; in vitro anticancer activity; indazole; Indolizine; nitrogen-containing heterocycle

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