Autophagy-regulating N-heterocycles derivatives as potential anticancer agents

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Pharmacology

Background:

• Autophagy plays a dual role in cancer, potentially suppressing or promoting tumor growth.
• Natural compounds modulating autophagy are increasingly recognized for their anti-cancer therapeutic potential.
• N-heterocycle derivatives are crucial scaffolds in drug discovery for novel therapeutics.

Purpose of the Study:

• To review and classify N-heterocycle derivatives with autophagy-regulating activities over the past decade.
• To analyze the structural characteristics, bioactivities, and mechanisms of these compounds.
• To identify promising drug candidates for antitumor therapy.

Main Methods:

• Systematic literature search for N-heterocycle derivatives with autophagy-regulating activities.
• Classification of 116 compounds into 12 structural categories.
• Analysis of reported bioactivities, mechanisms of action, and in vivo antitumor effects.

Main Results:

• 116 N-heterocycle derivatives with autophagy-regulating activities were identified and classified.
• Compounds were categorized into 12 distinct structural classes.
• Several compounds, including bisaminoquinoline (3), pancratistatin (8), and others, demonstrated significant in vivo antitumor activity.

Conclusions:

• N-heterocycle derivatives represent a valuable class of compounds for targeting cancer through autophagy modulation.
• Specific compounds exhibit potent in vivo antitumor efficacy, warranting further investigation as potential drug candidates.
• This review provides a comprehensive overview and highlights future directions in the field.