Therapeutic Potential of Indazole as a Promising Scaffold for Anticancer Drug Development: A Comprehensive Review

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Indazole scaffolds (1H- and 2H-) possess unique hydrogen-bonding properties and aromatic stability.
• These characteristics enable interaction with various oncogenic targets, making indazoles attractive for drug discovery.

Purpose of the Study:

• To review the structural features of indazole derivatives contributing to anticancer potential.
• To summarize recent biological evaluations and advances in indazole-based anticancer drug development.

Main Methods:

• Literature review of studies on indazole derivatives' anticancer activities.
• Analysis of structure-activity relationships, including computational studies.
• Discussion of biological evaluations (in vitro and in vivo) and patent landscape.

Main Results:

• Indazole derivatives exhibit diverse anticancer activities: kinase inhibition, cell-cycle arrest, apoptosis induction, DNA interaction, and oncogenic pathway modulation.
• Potent compounds show nano- to micromolar IC50 values, with strategic substitutions enhancing efficacy and selectivity.
• Key molecular targets include AURKs, CDKs, EGFR, FGFR, HIF-1, ER-α, MAPKs, and PDKs.

Conclusions:

• Indazole derivatives represent a promising scaffold for developing novel anticancer therapeutics.
• Structural optimization is crucial for improving potency and selectivity against cancer targets.
• Further research into indazole-based compounds could lead to innovative cancer treatments.