Synthesis and structure–activity relationship studies of mono- and bis-thiourea derivatives featuring halogenated azo dyes with antimicrobial properties

Abstract

A series of mono-substituted thiourea (2a–i) and bis-substituted thiourea-azo (3a–f) derived from paracetamol derivatives were prepared from isothiocyanates with one and two equivalents of halogenated azo dyes, respectively. The incorporation of azo-derived paracetamol via thiourea moiety in 2a–i depicted excellent microbial activity on Staphylococcus aureus, and 2-(((3-((2-bromophenyl)diazenyl)-4-hydroxyphenyl)carbamothioyl)carbamoyl)phenyl acetate, 2a showed equivalent inhibition properties to the standard ampicillin (10 mm). The structure–activity relationship studies of 2a were supported via molecular docking interaction against S. aureus tyrosyl-tRNA synthetase protein which displayed a free energy interaction of −7.7 kcal/mol compared to aspirin (−6.4 kcal/mol).