In Vitro β–Glucuronidase and In Silico Molecular Docking Studies of Thiazole-Fused-Thiadiazole Derivatives Prepared through Molecular-Iodine Promoted [3+2] Oxidative Cyclization

As pharmacological medicines and their constituents are vital to human life and global public health, there is a growing need to find safe and efficient inhibitors for the treatment of β-glucuronidase. The present study was aimed to design and synthesize thiazole-fused-thiadiazole derivatives (1-15). The synthesized compounds were spectroscopically characterized through elementary analysis, HREIMS, 1HNMR and 13CNMR. After the confirmation of their structure, the synthesized compounds were tested for their inhibition properties against β-glucuronidase (in vitro) as compared to standard D-saccharic acid-1,4- lactone drug. The tested derivatives exhibited variable inhibitory potential against β-glucuronidase with an IC50 values in the range of 1.20 ± 0.05 to 34.70 ± 0.70 µM. The results were compared with standard drug D-saccharic aci-1, 4-lactone (48.30 ± 0.50 µM). In particular, derivatives 3, 5, 7, 9, 11, 14 were found to be significantly active, even more active than the standard drug, while the remaining compounds showed moderate to low inhibitory potential compared to the standard drug. Structure-activity relationship (SAR) study was carried out for all analogues based on substitutions pattern around aromatic aryl rings. Similarly, molecular study was conducted to assess the binding interactions of synthesized derivatives with the active sites of target enzyme.