| Title: |
Computational Insights into the Structural Basis for Reduced Hepatotoxicity of Novel Nonopioid Analgesics |
| Authors: |
Coderch, Claire; Bazán, Hernan A; Bazan, Nicolas G; Surjyadipta, Bhattacharjee; Alvarez-Builla, Julio; de Pascual-Teresa, Beatriz |
| Source: |
School of Graduate Studies Faculty Publications |
| Publisher Information: |
LSU Health Digital Scholar |
| Publication Year: |
2025 |
| Subject Terms: |
N‐acetyl‐p‐benzoquinone imine; acetaminophen toxicity; docking; drug metabolism and pharmacokinetic; molecular dynamics; new chemical entities; novel non‐opioid analgesics; Chemical and Pharmacologic Phenomena; Digestive System; Medical Toxicology; Organic Chemicals |
| Description: |
Acetaminophen (ApAP) toxicity arises from the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI), a degradation product known to cause significant liver damage and kidney injury. This toxicity is a major concern associated with the widespread use of ApAP, a commonly used nonsteroidal anti-inflammatory drug. To address this important issue, a series of novel nonopioid analgesic candidates with reduced toxicity have been recently reported. However, the molecular and atomic-level mechanisms underlying their decreased toxicity remain largely unexplored. In this study, computational analyses is performed to investigate the dynamic behavior, physicochemical properties, and ligand-receptor interactions of these new chemical entities (NCEs). The findings provide a rational explanation for their differing toxicity profiles and contribute to a deeper understanding of their metabolic pathways. Based on these insights, compound 6 has emerged as a promising ApAP alternative and is currently under development. These investigations pave the way for designing novel hepatotoxicity-free NCE analgesics with improved drug metabolism and pharmacokinetic properties. |
| Document Type: |
text |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://digitalscholar.lsuhsc.edu/sogs_facpubs/447; https://digitalscholar.lsuhsc.edu/context/sogs_facpubs/article/1446/viewcontent/Computational_Insights_into_the_Structural_Basis_for_Reduced_Hepatotoxicity_of_Novel_Nonopiod_Analgesics.pdf |
| DOI: |
10.1002/cmdc.202500639 |
| Availability: |
https://digitalscholar.lsuhsc.edu/sogs_facpubs/447; https://doi.org/10.1002/cmdc.202500639; https://digitalscholar.lsuhsc.edu/context/sogs_facpubs/article/1446/viewcontent/Computational_Insights_into_the_Structural_Basis_for_Reduced_Hepatotoxicity_of_Novel_Nonopiod_Analgesics.pdf |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.41BF17A0 |
| Database: |
BASE |