Isatin-based oxime ethers as anticancer agents against human colorectal carcinoma

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Cancer Research

Background:

• Colorectal cancer is a leading cause of cancer-related mortality.
• Development of novel anticancer agents is crucial for effective treatment.
• Isatin derivatives have shown promise as anticancer compounds.

Purpose of the Study:

• To synthesize and evaluate new isatin-based oxime ethers for anticancer activity.
• To identify lead compounds with potent cytotoxic effects against colorectal cancer cells.
• To investigate the mechanism of action and safety profile of promising candidates.

Main Methods:

• Synthesis of novel isatin-based oxime ethers.
• Cytotoxicity assays (MTT, Trypan Blue) against HCT116 colon cancer cells.
• Cellular morphology, apoptosis assays (Hoechst/PI, AO/PI staining).
• Colony formation and migration assays.
• In-silico molecular docking studies against Human Tankyrase-2 and Bruton's tyrosine kinase.

Main Results:

• Compound 10d exhibited significant cytotoxicity against HCT116 cells (IC50 = 22.31 µM).
• Compound 10d demonstrated a favorable safety profile against normal HEK cells.
• Morphological changes, apoptosis induction, and reduced colony formation/migration were observed.
• Molecular docking revealed high binding affinity of compound 10d to Human Tankyrase-2 (5BXU) and Bruton's tyrosine kinase (7LTZ).

Conclusions:

• Compound 10d is a promising lead anticancer agent for colorectal cancer.
• Its mechanism may involve targeting Human Tankyrase-2 and Bruton's tyrosine kinase.
• Further derivatization of compound 10d is warranted for enhanced therapeutic potential.