Bioisosteric Replacement of Amide Group with 1,2,3-Triazoles in Acetaminophen Addresses Reactive Oxygen Species-Mediated Hepatotoxic Insult in Wistar Albino Rats

Acetaminophen (AP) is the most popularly recommended over the counter analgesic antipyretic in clinical use. However the drug is handicapped by the occurrence of hepatotoxic insult following acute ingestion. Consequently AP induced hepatotoxicity is often implicated in accidental or suicidal overdose. In the current study, we investigated the potential of bioisosteric replacement of amide in AP with 1,2,3-triazoles in curbing AP induced hepatotoxicity. The therapeutic utility of synthesized bioisosteres was established by careful tailoring and optimization of the synthetic methodology along with detailed toxicological testing of pharmacologically potent APTCs (Acetaminophen triazole conjugates) conjugate. In lieu with the same, we herein report a series of novel 17 APTCs synthesized via aromatic substitution using sodium azide, L-proline and copper iodide followed by clicking it with substituted alkynes using copper sulphate and sodium ascorbate. Pharmacological evaluation revealed out of the series of 17...