Title: In silico analysis of multiple targets (HER2 receptor and DNA) inhibition by natural isoquinoline derivatives for breast cancer treatment

Authors: Lokesh Kumar Agarwal

Addresses: Department of Chemistry, Mohanlal Sukhadia University, Udaipur-313001, India

Abstract: Breast cancer is one of the major challenges for women's health worldwide. Approximately 15-30% of breast cancer aggressiveness is caused by over-reactivity of the HER2 receptor enzyme. Hence, the inhibition of HER2 has become a promising approach for the treatment of human breast cancer. In this in silico study, the binding interactions of five natural isoquinoline derivatives with the HER2 enzyme (PDB Id 3PPO) and double-stranded DNA (PDB Id 1Z3F) were investigated. The average binding free energy of ligands with HER2 and DNA receptors ranges from -8.52 kcal/mol to -6.59 kcal/mol and from -9.76 kcal/mol to -6.47 kcal/mol respectively. The drug-likeness competency of ligand molecules was also investigated using the Lipinski rule of five (Ro5). Lamellarin A5 was found to show better inhibition strength for both targets as compared to reference compounds (Neratinib & Afatinib) with improved drug-likeness properties. The outcomes of the study suggest Lamellarin A5 for further in vitro/in vivo analysis.

Keywords: breast cancer; HER2; isoquinoline derivatives; molecular docking; pharmacology.

DOI: 10.1504/IJCBDD.2022.128239

International Journal of Computational Biology and Drug Design, 2022 Vol.15 No.3, pp.155 - 171

Received: 10 Mar 2022
Accepted: 04 Jul 2022
Published online: 12 Jan 2023 *

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