Plant-Derived Anticancer Candidates Targeting mTOR, EGFR, HER2: Insights From Molecular Docking and Dynamics...

Area of Science:

• Pharmacology and Natural Products Chemistry
• Oncology
• Molecular Biology

Background:

• Mammalian target of rapamycin (mTOR) is crucial in intracellular signaling and a target for breast cancer therapy.
• Growth factor receptors like EGFR and HER2 influence mTOR signaling.
• Natural products offer a promising source for novel anti-cancer agents.

Purpose of the Study:

• To identify novel, safe breast cancer inhibitors from Meehania fargesii var. Radicans using natural products.
• To evaluate the anti-proliferative effects of selected compounds on MCF-7 breast cancer cells.
• To investigate the molecular interactions of potent compounds with key cancer-related targets.

Main Methods:

• Structure-based virtual screening and molecular docking of 30 compounds from Meehania fargesii var. Radicans.
• In vitro anti-MCF-7 proliferation assays to determine IC50 values.
• Molecular dynamics simulations to analyze compound-target interactions.

Main Results:

• Compound 28 (nepetoidin B) demonstrated the most potent inhibition of MCF-7 proliferation with an IC50 of 8.47 ± 0.85 µM.
• Molecular dynamics simulations confirmed stable binding of nepetoidin B to mTOR, HER2, and EGFR.
• Compounds 26-30 showed significant inhibitory effects, with compound 28 being the most effective.

Conclusions:

• Nepetoidin B is a promising natural product-derived inhibitor for breast cancer therapy.
• Targeting mTOR, HER2, and EGFR pathways with nepetoidin B offers a potential therapeutic strategy.
• Meehania fargesii var. Radicans is a valuable source for discovering novel anti-cancer compounds.