Synthesis, anticancer, structural, and computational docking studies of 3-benzylchroman-4-one derivatives

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Cancer remains a leading cause of mortality worldwide, necessitating the development of novel therapeutic agents.
• Chroman-4-one derivatives have demonstrated a range of biological activities, including anticancer properties.

Purpose of the Study:

• To synthesize a series of 3-Benzylchroman-4-one compounds.
• To evaluate the in vitro anticancer activity of these synthesized compounds against human breast carcinoma (BT549) and cervical carcinoma (HeLa) cell lines.
• To investigate the structure-activity relationships and potential mechanisms of action.

Main Methods:

• Synthesis of 3-Benzylchroman-4-one derivatives using established organic chemistry protocols.
• Anticancer activity screening using the MTT assay against BT549, HeLa, and Vero (normal kidney epithelial) cell lines.
• Determination of IC50 values to quantify compound potency.
• Single crystal X-ray crystallography for structural elucidation of key compounds (3h, 3i).
• Molecular docking studies of lead compounds with the tumor suppressor protein p53.

Main Results:

• Several 3-Benzylchroman-4-one derivatives were successfully synthesized.
• Compound 3b exhibited significant activity against BT549 cells with an IC50 of 20.1 µM.
• Compound 3h demonstrated potent activity against HeLa cells with an IC50 of 20.45 µM and moderate activity against BT549 cells (IC50 = 42.8 µM).
• The molecular structures of 3h and 3i were confirmed by X-ray crystallography.
• Molecular docking suggested potential interactions between compound 3h and the p53 protein.

Conclusions:

• The synthesized 3-Benzylchroman-4-one derivatives represent a promising class of anticancer agents.
• Compounds 3b and 3h display selective and potent activity against specific cancer cell lines, warranting further investigation.
• Structural and computational studies provide insights into the potential mechanism of action, particularly the interaction with p53.