New chromene-based 1-aryl-1 <i>H</i> -pyrazole-3-carboxylate hybrids linked to 1,3,4-oxadiazole and/or arene units with potential bacterial and DNA gyrase inhibitory potency

For both organic and bioorganic chemists, the search for novel DNA gyrase inhibitors is a crucial strategy for managing bacterial infections. In this study, we developed a facile [3 + 2] cycloaddition protocol for the synthesis of new chromene-pyrazole hybrids 1 and 2 linked to 1,3,4-oxadiazole and/or arene units with potential antibacterial and anti-DNA gyrase potency. The protocol involved reacting the proper chromene-based enaminones with the suitable hydrazonyl chlorides in refluxing dioxane containing an equimolar amount of triethylamine for 6–10 h. Generally, hybrids 2a–2d, attached to a 1,3,4-oxadiazole unit, demonstrated 2-fold more potency compared to their analogues 1a–1d. The 1,3,4-oxadiazole-linked chromene-pyrazole 2d, attached to a 4-nitrophenyl group at pyrazole-N1, demonstrated the best antibacterial potency with an MIC/MBC of 1.25/2.50 µM against S. aureus and E. faecalis and an MIC/MBC of 2.50/10.00 µM against MRSA strains. Additionally, 2d showed promising inhibitory potency against S. aureus DNA gyrase with IC50 of 2.125 μM.