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<p>A series of novel indazole derivatives (compound I-X) were designed, synthesized, and evaluated as potential cyclin dependent kinase 2 (CDK2) inhibitors with anticancer activity. The compounds were characterized using spectroscopic techniques and assessed for their in vitro CDK2 inhibitory potential and cytotoxic activity against MCF-7 breast cancer cells using roscovitine, doxorubicin, and 5-fluorouracil as standard reference drugs. Compounds IV and VIII emerged as the most potent, with IC<sub>50</sub> values of 22.75 µM and 24.38 µM against MCF-7 cells, and 22.45 µM and 29.23 µM against CDK2, respectively. Molecular docking studies revealed key ligand-protein interactions within the CDK2 active site, including hydrogen bonding, hydrophobic interactions, π-π stacking, and halogen bonding with residues such as ASN132, LYS33, ILE10, VAL18, and LEU134. Molecular dynamics simulations were also conducted for the lead compound. In silico ADME and toxicity predictions indicated favourable drug-like properties for most compounds, with acceptable pharmacokinetic profiles and minimal toxicity risks. While the synthesized compounds exhibited lower potency compared to the standard CDK2 inhibitor, their competitive activity profiles and dual-targeting nature warrant further optimization. This study highlights the potential of indazole scaffolds as CDK2 inhibitors and provides a foundation for future research aimed at developing novel anticancer agents.</p> Graphical abstract <p></p>

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Indazole-Based Small Molecules as Cyclin-Dependent Kinase-2 Inhibitors: Synthesis, In Vitro Anticancer Evaluation, and Molecular Docking Studies

  • 期刊论文

  • 发表日期：

    2026年6月16日

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  • Vinod Ashtekar,
  • Ashish Patel,
  • Drashti Shah,
  • Ranjitsinh C. Dabhi,
  • Chetan B. Sangani,
  • Nishith Teraiya,
  • Arjun S. Chaudhari,
  • Vatsal Chaudhari,
  • Hemant N. Patel

摘要

A series of novel indazole derivatives (compound I-X) were designed, synthesized, and evaluated as potential cyclin dependent kinase 2 (CDK2) inhibitors with anticancer activity. The compounds were characterized using spectroscopic techniques and assessed for their in vitro CDK2 inhibitory potential and cytotoxic activity against MCF-7 breast cancer cells using roscovitine, doxorubicin, and 5-fluorouracil as standard reference drugs. Compounds IV and VIII emerged as the most potent, with IC50 values of 22.75 µM and 24.38 µM against MCF-7 cells, and 22.45 µM and 29.23 µM against CDK2, respectively. Molecular docking studies revealed key ligand-protein interactions within the CDK2 active site, including hydrogen bonding, hydrophobic interactions, π-π stacking, and halogen bonding with residues such as ASN132, LYS33, ILE10, VAL18, and LEU134. Molecular dynamics simulations were also conducted for the lead compound. In silico ADME and toxicity predictions indicated favourable drug-like properties for most compounds, with acceptable pharmacokinetic profiles and minimal toxicity risks. While the synthesized compounds exhibited lower potency compared to the standard CDK2 inhibitor, their competitive activity profiles and dual-targeting nature warrant further optimization. This study highlights the potential of indazole scaffolds as CDK2 inhibitors and provides a foundation for future research aimed at developing novel anticancer agents.

Graphical abstract