Design of Potent Telomerase Inhibitors using Ligand-based Approaches and Molecular Dynamics Simulations Studies

Area of Science:

• Medicinal Chemistry
• Computational Drug Design

Background:

• Telomerase is a key target for cancer therapy.
• Ligand-based approaches are employed to design novel anticancer agents.

Purpose of the Study:

• To design potent telomerase inhibitors for cancer therapy.
• To identify potential drug candidates with favorable pharmacokinetic and toxicity profiles.

Main Methods:

• Generation of a ligand-based pharmacophore model for oxadiazole derivatives.
• Virtual screening of the ZINC database using the pharmacophore model.
• Molecular docking, pharmacokinetic, and toxicity predictions (pkCSM, SwissADME).
• Molecular dynamics simulations with MM-PBSA binding free energy calculations (GROMACS).

Main Results:

• A pharmacophore model with two hydrophobic and three aromatic features was developed.
• MM-PBSA calculations confirmed the stability of protein-ligand complexes.
• Two in-silico compounds (ZINC82107047 and ZINC8839196) exhibited good predicted properties.

Conclusions:

• ZINC82107047 and ZINC8839196 are identified as hit molecules for further investigation.
• These compounds show potential for developing safe and potent telomerase inhibitors for cancer treatment.