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Sulfonamide‐β‐lactam Hybrids Incorporating the Piperazine Moiety as Potential Antiinflammatory Agent with Promising Antibacterial Activity
Author(s) -
Heiran Roghayeh,
Jarrahpour Aliasghar,
Riazimontazer Elham,
Gholami Ahmad,
Troudi Azza,
Digiorgio Carole,
Brunel Jean Michel,
Turos Edward
Publication year - 2021
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202101194
Subject(s) - chemistry , piperazine , active site , moiety , docking (animal) , in silico , stereochemistry , combinatorial chemistry , in vivo , antibacterial activity , cycloaddition , biological activity , lactam , staudinger reaction , ketene , sulfonamide , in vitro , biochemistry , medicinal chemistry , enzyme , organic chemistry , biology , bacteria , medicine , genetics , nursing , microbiology and biotechnology , gene , catalysis
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 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. 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.