A Short Review on Biological Activities of Paracetamol Derivatives

Abstract

Paracetamol reduces body temperature with multiple mechanisms. Paracetamol is chemically 4-hydroxy acetanilide and has a good safety profile. Following its successful use as an over-the-counter antipyretic and analgesic medication, several attempts were made to increase the potency, mask the bitter taste, and decrease the toxicity of this drug by modifications at the phenyl ring, acetamido group, and hydroxyl group. The free hydroxyl group of paracetamols was masked to obtain prodrugs (carbonate prodrugs, ester prodrugs like alanine-prodrug, proline-prodrug, galactosylated prodrug, and mutual prodrugs with other drugs and NSAIDs). Propacetamol is a commercially available prodrug derived from paracetamol that is effective in parenteral form. Paracetamol ester prodrugs with sulfur-containing amino acids such as N-acetyl cysteine, cysteine, and methionine showed low hepatotoxicity compared to the parent drug. In addition, paracetamol derivatives including metal complexes, chalcones, Mannich bases, nucleoside analogs, hybrids with the aryl-imidazolidinyl ring, thymol, and triazole ring displayed diverse activities like antioxidant, anticancer, and antimicrobial activities.

Exploring acetaminophen prodrugs and hybrids: a review

“…Moreover, novel designs of APA hybrids can raise perspective and make compounds easy to prepare with antioxidant, antimicrobial, antibacterial, and antitumor properties. 163,164 A suitable combination of the APAP core with scaffolds from natural products like artemisinin or its derivatives (APAP–dihydroartemisinin molecule, an O-modified APAP prodrug) 165 can also allow refilling the arsenal of needed drugs.…”