Title:Design, Synthesis, Biological and in silico Evaluation of Novel Indazole-pyridine Hybrids for the Treatment of Breast Cancer
Volume: 21
Issue: 2
Author(s): Ishan Panchal*, Rati Kailash Prasad Tripathi, Mange Ram Yadav, Meet Valera and Kinjal Parmar
Affiliation:
- Department of Pharmaceutical Chemistry, Parul Institute of Pharmacy, Parul University, Vadodara, Gujarat, 391760,
India
- Department of Pharmaceutical Chemistry, Arihant School of Pharmacy and Bio-Research Institute, Gandhinagar,
Gujarat, 382421, India
Keywords:
Breast cancer, indazole-pyridine hybrids, cytotoxicity, molecular docking, tropomyosin receptor kinase A, in silico pharmacokinetic studies.
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 (5a-h) 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, in silico 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. in silico physicochemical
and pharmacokinetic predictions were made to assess the compounds’ drug-like
properties.
Results: Compound 5a emerged as the most active compound among the others with GI50 < 10
μg/ml. Besides, compound 5a 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. in silico physicochemical and pharmacokinetic prediction studies indicated
that compound 5a obeyed both Lipinski’s and Veber’s rule and displayed a versatile
pharmacokinetic profile, implying compound 5a 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 anticancer
agents. Further optimization and preclinical development are necessary to advance these
compounds to clinical trials.
