Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 μM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.

Department of Biotechnology and Biochemistry The Islamia University of Bahawalpur Bahawalpur 63100 Pakistan

Department of Chemistry Government College University Faisalabad Faisalabad 38000 Pakistan

Department of Chemistry Government Sadiq Women University Bahawalpur 63100 Pakistan

Department of Chemistry Islamia College University Peshawar Peshawar 25120 Pakistan

Department of Chemistry The Islamia University of Bahawalpur Bahawalpur 63100 Pakistan

Department of Chemistry The Women University Multan 66000 Pakistan

Department of Pharmaceutics College of Pharmacy King Saud University Riyadh 11451 Saudi Arabia

Institute of Chemistry University of Sargodha Sargodha 40100 Pakistan

Skin Barrier Research Group Faculty of Pharmacy in Hradec Králové Charles University 500 05 Hradec Králové Czech Republic

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