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

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 antiinflammatory 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.

Prevention of Postsurgical Abdominal Adhesion Using Electrospun TPU Nanofibers in Rat Model

“…Staphylococcus aureus and Escherichia coli , as two pathogenic microorganisms, were selected for the antibacterial assay of TPU according to Heiran et al [ 31 ]. The organisms were suspended in freshly prepared Mueller-Hinton's broth (MHB) at a standard concentration of 0.5 McFarland and diluted with a 1 : 20 proportion by MHB.…”

C7‐Halomethylene/methyl‐C3‐thiophenyl‐spirocyclic‐β‐lactams: Synthesis, X‐ray Analysis, Antimicrobial Evaluation, Cytotoxicity Profile and Molecular Docking Interactions

“…[21] In the contemporary landscape of pharmaceutical research and innovation, multiple research groups are investigating spirocyclic-β-lactam hybrid heterocyclic skeletons that have been pharmacokinetically optimized, showcasing promise as prospective candidates for novel antibacterial agents. [22][23][24][25][26][27][28][29] In the field of antimicrobial compounds, synthetic variations often exhibit a unique heterocyclic pharmacophore. The significance of heterocyclic rings in drug design, highlighted by the Food and Drug Administration (FDA) databases, underscores their pivotal role in medicinal chemistry due to their adaptable nature.…”

“…In the contemporary landscape of pharmaceutical research and innovation, multiple research groups are investigating spirocyclic‐β‐lactam hybrid heterocyclic skeletons that have been pharmacokinetically optimized, showcasing promise as prospective candidates for novel antibacterial agents [22–29] . In the field of antimicrobial compounds, synthetic variations often exhibit a unique heterocyclic pharmacophore.…”

Molecular Docking and Antibacterial Assessment of Monocyclic β‐Lactams against Broad‐Spectrum and Nosocomial Multidrug‐Resistant Pathogens

“…For example, Ezetimibe (Zetia) is a prescribed lipid‐lowering drug that selectively reduces the intestinal absorption of cholesterol [10] . They have also been reported to exhibit potent pharmacological activates such as anticancer, [11] antifungal, [9c,11c] antioxidant, [11a,b,d] anti‐inflammation, [9a,12] anti‐HIV, [13] antidepressant, [14] antitubercular, [15] antiurease, [16] antimalaria, [17] acetylcholinesterase inhibitor, [18] carbonic anhydrase inhibitor, [18b,19] K562 human leukemia cell line inhibitor, [11d] and NAAA inhibitor [20] . Moreover, they consist of a building block to synthesize different pharmacologically active compounds [5a,21] .…”