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Volume 21, Issue 2
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Introduction

The prevalence of breast cancer presents a substantial global health concern, underscoring the ongoing need for the development of inventive therapeutic remedies.

Methods

In this investigation, an array of novel indazole-pyridine hybrids () have been designed and synthesized to assess their potential as candidates for treating breast cancer. Subsequently, we have conducted biological evaluations to determine their cytotoxic effects on the human MCF-7 breast cancer cell line. Furthermore, analysis was conducted to estimate the inhibition potential of the compounds against TrkA (Tropomyosin receptor kinase A), a specific molecular target associated with breast cancer, through molecular docking. physicochemical and pharmacokinetic predictions were made to assess the compounds’ drug-like properties.

Results

Compound emerged as the most active compound among the others with GI50 < 10 μg/ml. Besides, compound showed high binding energy (BE -10.7 kcal/mol) against TrkA and was stabilized within the TrkA binding pocket through hydrophobic, H-bonding, and van der Waals interactions. physicochemical and pharmacokinetic prediction studies indicated that compound obeyed both Lipinski’s and Veber’s rule and displayed a versatile pharmacokinetic profile, implying compound to appear as a viable candidate and that it could be further refined to develop therapeutic agents for potentially treating breast cancer.

Conclusion

This study offers a promising direction for the advancement of innovative breast cancer treatments, highlighting the effectiveness of indazole-pyridine hybrids as potential anti-cancer agents. Further optimization and preclinical development are necessary to advance these compounds to clinical trials.

© 2025 Bentham Science Publishers
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2024-08-06
2025-04-15

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Design, Synthesis, Biological and in silico Evaluation of Novel Indazole-pyridine Hybrids for the Treatment of Breast Cancer
Curr. Computeraided Drug Des. 21, 211 (2025); https://doi.org/10.2174/0115734099308839240724100224
/content/journals/cad/10.2174/0115734099308839240724100224
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  • Article Type:     Research Article
Keyword(s): Breast cancer; cytotoxicity; in silico pharmacokinetic studies; indazole-pyridine hybrids; molecular docking; tropomyosin receptor kinase A

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