A Promising Approach to Target Colorectal Cancer Using Hybrid Triarylmethanes

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Research

Background:

• Colorectal cancer (CRC) remains a significant global health challenge.
• Development of novel, effective, and less toxic anti-cancer agents is crucial.
• Hybrid molecules offer a promising strategy for drug discovery.

Purpose of the Study:

• To design and synthesize innovative hybrid triarylmethane compounds as potential anti-colorectal cancer agents.
• To evaluate the antiproliferative activity and cytotoxicity of synthesized compounds.
• To identify potential molecular targets and assess drug-likeness properties.

Main Methods:

• Synthesis of hybrid triarylmethanes and N-oxide analogues using ethylene glycol or lysine spacers.
• Antiproliferative assays on human HT-29 and HCT116 colorectal cancer cell lines.
• Cytotoxicity assessment on murine fibroblasts.
• Molecular docking studies targeting protein kinase B (AKT).
• Computational drug-likeness evaluation.

Main Results:

• Successful synthesis of hybrid triarylmethane and N-oxide compounds.
• Three pyridine N-oxide analogs exhibited potent antiproliferative activity (IC50: 18-24 μM) against CRC cell lines.
• Active compounds showed no significant toxicity to murine fibroblasts at effective concentrations.
• AKT was identified as a potential molecular target.
• Favorable oral and intestinal absorption predicted computationally.

Conclusions:

• Novel hybrid triarylmethane N-oxide analogs demonstrate significant anti-colorectal cancer potential.
• These compounds exhibit a favorable safety profile, warranting further investigation.
• Targeting AKT and possessing good drug-likeness properties make them promising candidates for further preclinical development.