In Silico and In Vitro Analyses of Strawberry-Derived Extracts in Relation to Key Compounds' Metabolic and Anti-Tumor...

Area of Science:

• Pharmacology and Natural Products Chemistry
• In silico and in vitro drug discovery
• Medicinal chemistry of plant-derived compounds

Background:

• Plant extracts contain numerous understudied small molecules with therapeutic potential.
• Phloridzin, phloretin, and 4-methylchalcone are key compounds in strawberry extracts.
• Investigating these compounds' properties and interactions is crucial for drug development.

Purpose of the Study:

• To evaluate the in silico physicochemical, pharmacokinetic, and drug-likeness properties of phloridzin derivatives and strawberry compounds.
• To assess the potential of these compounds to interfere with P-glycoprotein (P-gp) and cytochrome P450 (CYP) enzymes.
• To determine the in vitro cytoprotective and anti-proliferative activities of strawberry extract (S) and phloridzin derivatives.

Main Methods:

• In silico analysis of physical-chemical, pharmacokinetic, and drug-likeness properties.
• Assessment of inhibitory potential against P-gp, CYP enzymes, Bcl-2, TNKS1, and COX-2.
• In vitro Caco-2 cell studies evaluating cytoprotective and anti-proliferative effects of compounds and combinations.

Main Results:

• Phloretin (Phl) demonstrated potential for supporting human intestinal cell health, alone or with strawberry extract (S).
• Phloridzin (Phd) and its combination with S were ineffective; 4-methylchalcone (4-MeCh) alone showed enhanced anticancer activity.
• In silico studies indicated that phloridzin derivatives might interact with major CYP enzymes, posing practical limitations.

Conclusions:

• Phloretin is a promising candidate for promoting intestinal health.
• 4-methylchalcone exhibits potential as an adjunct in anticancer drug combinations.
• Phloridzin derivatives require careful consideration due to potential CYP enzyme interactions, limiting their clinical application.