Chlordiazepoxide against signalling, receptor and regulatory proteins of breast cancer: a structure-based in-silico approach

In this study, we included four crucial proteins that perform signalling, receptor, and regulatory action, namely- NUDIX Hydrolases, Dihydrofolate Reductase, HER2/neu Kinase and EGFR and performed multitargeted molecular docking studies against human-approved drugs using HTVS, SP and extra precise algorithms and filtered the poses with MM\GBSA, suggested a benzodiazepine derivative chlordiazepoxide, used as an anxiolytic agent, can be a multitargeted inhibitor with docking and MM\GBSA score ranging from - 4.628 to - 7.877 and - 18.59 to - 135.86 kcal/mol, respectively, and the most interacted residues were 6ARG, 6GLU, 3TRP, and 3VAL. The QikProp-based ADMET and DFT computations showed the suitability and stability of the drug candidate followed by 100 ns MD simulation in water and MMGBSA on trajectories, resulting in stable performance and many intermolecular interactions to make the complexes stable, which favours that chlordiazepoxide can be a multitargeted breast cancer inhibitor. However, experimental validation is needed before its use.PMID:38630325 | DOI:10.1007/s12032-024-02366-w

Source: Molecular Medicine - April 17, 2024 Category: Molecular Biology Authors: Ahad Amer Alsaiari Amal F Gharib Maha Mahfouz Bakhuraysah Amani A Alrehaili Shatha M Algethami Hayfa Ali Alsaif Norah Al Harthi Mohammed Ageeli Hakami Source Type: research