Targeting telomeric RNA quadruplexes with natural metabolites to prevent cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Cancer cells achieve immortality through telomerase maintenance of telomeric repeats.
• Telomeric G-quadruplex (RG4) structures are key targets for inhibiting telomerase activity.
• Natural products offer a promising avenue for novel cancer therapeutic development.

Purpose of the Study:

• To screen non-nucleoside mushroom metabolites for their ability to stabilize RG4 structures.
• To investigate the molecular interactions and binding affinities of selected metabolites with RG4.
• To evaluate the therapeutic potential of these compounds in cancer treatment.

Main Methods:

• Molecular docking using AutoDock Vina to predict binding interactions.
• Molecular dynamics simulations (250 ns) using GROMACS to assess complex stability.
• Binding free energy calculations to quantify interaction strength.

Main Results:

• Sterenin M, Melleolide K, and Zhankuic Acid A demonstrated strong binding affinity to RG4 structures.
• These metabolites exhibited significant non-covalent interactions with RG4 at the atomic level.
• Molecular dynamics simulations confirmed the stability of the RG4-metabolite complexes.

Conclusions:

• The studied mushroom metabolites show promise as novel anticancer agents by targeting telomeres.
• Further in vitro and in vivo studies are warranted to determine toxicity, efficacy, and optimal dosage.
• These compounds could potentially be developed into new therapeutic strategies for cancer treatment.