Sulfonamide-β-lactam Hybrids Incorporating the Piperazine Moiety as Potential Antiinflammatory Agent with Promising Antibacterial Activity

摘要

Several monocyclic β-lactams have been synthesized via a [2 + 2] ketene-imine cycloaddition reaction (Staudinger reaction) and evaluated for their biological activities. The structure of synthesized products was confirmed by spectral data and elemental analyses. β-Lactams 4b and 4h exhibited 31 and 27 anti-inflammatory ratios, respectively, which are as well as the well-known dexamethasone corticosteroid with a 32 antiinflammatory ratio. The two most active compounds 4b and 4h showed IC_(50) values more than 200 μM against the HepG2 cell line, in comparison with doxorubicin (IC_(50)<1 μM), indicated biocompatibility and nontoxic behavior. 4d, 4j, 4k, and 4l, were active against S. aureus and E. coli and had broad spectrum property. The tested compounds were subjected to in silico prediction of pharmacokinetics properties (ADMET) to assess the potential in vivo effectiveness. The molecular docking study confirmed that the active inhibitors 4b and 4h are well fitted in the iNOS active site. This data suggests that 4b and 4h could potentially serve as effective iNOS inhibitors, a represent promising lead compounds for treating inflammatory disorders.