Synthesis, docking and evaluation of in vitro anti-inflammatory activity of novel morpholine capped β-lactam derivatives

Abstract

This study reports the synthesis and biological investigation of three series of novel -lactams bearing a morpholine substituent of the nitrogen center. These products were synthesized via Staudinger's [2+2]-ketene-imine cycloaddition reaction. The cycloadducts were fully characterized by spectral data, including 1 H-NMR, 13 C-NMR, IR, mass spectroscopy and elemental analyses, and then evaluated for anti-inflammatory activity. A number of the derivatives demonstrated higher therapeutic ratios than dexamethasone and corticosteroid medication. In silico molecular docking experiments showed a good correlation between the experimental activity and the calculated binding affinity to human inducible nitric oxide synthase, the enzymatic target for the anti-inflammatory response.

Antibacterial Effects of Green-Synthesized Silver Nanoparticles Using Ferula asafoetida against Acinetobacter baumannii Isolated from the Hospital Environment and Assessment of Their Cytotoxicity on the Human Cell Lines

“…The cells were incubated again for 24 hours, and 25 μL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) solution was added to each well and incubated for four hours. To solubilize MTT-formazan crystals, 100 μL of dimethyl sulfoxide (DMSO) was added to the mixture and shaken for ten minutes [19]. An ELISA plate reader (BioTek, Winooski, VT, USA) was also utilized to calculate the absorbance of each well at a wavelength of 540 nm, compared to the equivalent well of untreated cells.…”

Recent Advances in the Synthesis of Spiro‐β‐Lactams and Spiro‐δ‐Lactams

“…[25] Tosyl chloride was also used for xanthene-9-carboxylic acid (32) activation, with this approach leading to the synthesis of C3 spiro-β-lactams 34 g,i bearing a morpholine ring, in moderate to good yields (41-71%) (Scheme 8d). [26] The same group reported the use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (37, EEDQ) as the carboxylic acid activator for the in situ generation of ketene 38 (Scheme 9). [27] Spiro-xanthene spiro-β-lactams 34 j and 34 k were obtained in 80% and 84% yield, respectively.…”

“…The same type of spiro‐β‐lactams 34 e,f could also be prepared in good yields (70–72%) via cyclocondensation of xanthene‐9‐carboxylic acid ( 32 ) and aromatic imines in the presence of tosylimidazole ( 35 ) (Scheme 8c) [25] . Tosyl chloride was also used for xanthene‐9‐carboxylic acid ( 32 ) activation, with this approach leading to the synthesis of C3 spiro‐β‐lactams 34 g,i bearing a morpholine ring, in moderate to good yields (41–71%) (Scheme 8d) [26] …”

New Cassane Diterpenoids from the Seed Kernels of Caesalpinia cucullata, Exhibit Anti‐inflammatory Effect in vitro by Inhibiting iNOS Enzymatic Activity

“…NO is continuously overproduced when iNOS is activated by pro‐inflammatory cytokines and/or bacterial lipopolysaccharide in macrophages. [ 2‐3 ] Excessive NO, as a pro‐inflammatory mediator, can actively mediate rheumatoid arthritis, asthma, septic shock and chronic obstructive pulmonary disease and other inflammatory diseases. [ 4 ] Therefore, inhibiting the activity of the iNOS to block excessive NO production has been recognized as a promising strategy for the treatment of inflammatory diseases.…”