Sulfonamide‐β‐lactam Hybrids Incorporating the Piperazine Moiety as Potential Antiinflammatory Agent with Promising Antibacterial Activity. Issue 21 (7th June 2021)

• Record Type: Journal Article
• Authors: Heiran, Roghayeh; Jarrahpour, Aliasghar; Riazimontazer, Elham; Gholami, Ahmad; Troudi, Azza; Digiorgio, Carole; Brunel, Jean Michel; Turos, Edward
• Is Part Of: ChemistrySelect. Volume 6:Issue 21(2021)
• Page Start: 5313
• Page End: 5319
• Publication Date: 2021-06-07
• Subjects: ADMET -- 2-Azetidinone -- Biological activity -- Cycloaddition -- In silico.; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202101194
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: 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 4 b and 4 h exhibited 31 and 27 anti‐inflammatory ratios, respectively, which are as well as the well‐known dexamethasone corticosteroid with a 32 anti‐inflammatory ratio. The two most active compounds 4 b and 4 h showed IC50 values more than 200 μM against the HepG2 cell line, in comparison with doxorubicin (IC50 <1 μM), indicated biocompatibility and nontoxic behavior. 4 d, 4 j, 4 k, and 4 l, 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 4 b and 4 h are well fitted in the iNOS active site. This data suggests that 4 b and 4 h could potentially serve as effective iNOS inhibitors, a represent promising lead compounds for treating inflammatory disorders. Abstract : Some newly sulfonamide‐ β ‐lactam hybrids incorporating the piperazine moiety were synthesized and their biological activities were evaluated. Two derivatives demonstrated a similar therapeutic ratio to dexamethasone. Four derivatives showed good antibacterial activity against either E. coli and S. aureus in comparison with ampicillin as a standard, and all compounds showed low cytotoxicity towards HepG2 cell line. Moreover, molecular docking analysis supported the in vitro results.