Spice components as modulating agents of P-glycoprotein - An in silico study

Area of Science:

• Pharmacology
• Biochemistry
• Natural Products Chemistry

Background:

• P-glycoprotein (P-gp) is a key transporter protein involved in drug disposition and resistance.
• Overexpression of P-gp reduces drug absorption and efficacy, contributing to multidrug resistance (MDR).
• Natural compounds offer potential for developing novel P-gp inhibitors to overcome MDR.

Purpose of the Study:

• To identify natural phytochemicals from spices that can inhibit P-glycoprotein.
• To evaluate the drug-like properties and binding affinities of selected phytochemicals.
• To explore the potential of these compounds in modulating multidrug resistance.

Main Methods:

• Screening and selection of 33 phytochemicals from 25 spices.
• In silico analysis including absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction using pkCSM, Molinspiration, and SwissADME.
• Molecular docking and molecular dynamic simulations using BIOVIA Discovery Studio.
• Comparison with the reference drug verapamil.

Main Results:

• All 33 selected phytochemicals demonstrated P-gp inhibitory potential comparable to verapamil.
• Pandamarilactone-31 exhibited the highest binding affinity to P-glycoprotein.
• Other notable inhibitors include α-D-fructofuranoside methyl, sesamolinol, and nigellidine.

Conclusions:

• Natural phytochemicals from spices can serve as effective P-glycoprotein inhibitors.
• Pandamarilactone-31 is identified as a lead compound for developing novel MDR modulators.
• This study provides a foundation for further investigation into spice-derived compounds for therapeutic applications in MDR.