Functionalized Indolizines as Potential Anticancer Agents: Synthetic, Biological and In Silico Investigations

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Research

Background:

• Indolizine derivatives are recognized for their diverse biological activities.
• Developing novel anticancer agents with improved efficacy and safety profiles remains a critical challenge in oncology.

Purpose of the Study:

• To design and synthesize novel indolizine derivatives as potential anticancer agents.
• To evaluate the in vitro anticancer activity and in silico properties of the synthesized compounds.

Main Methods:

• Synthesis of indolizine derivatives via 1,3-dipolar cycloaddition of pyridinium N-ylides to ethyl propiolate.
• In vitro anticancer screening against the National Cancer Institute (NCI) 60 human tumor cell line panel.
• Molecular docking studies targeting the colchicine-binding site of tubulin and in silico ADMET analysis.

Main Results:

• Three series of indolizines (5a-f, 6a-f, 7a-g) were successfully synthesized and characterized.
• Compounds 5c, 6c, and 7g demonstrated significant inhibitory and cytotoxic effects against lung, brain, renal cancer, and melanoma cell lines.
• Molecular docking revealed strong binding affinities to tubulin, and in silico ADMET predictions indicated good oral bioavailability and low toxicity.

Conclusions:

• The synthesized indolizine derivatives represent promising candidates for anticancer drug development.
• Compounds 5c, 6c, and 7g warrant further investigation as potential therapeutic agents for various cancers.
• The study highlights the potential of indolizine scaffolds in the design of novel anticancer drugs.