Synthesis, In Vitro Anti-Inflammatory Activity, and HRMS Analysis of New Amphetamine Derivatives

Abstract

Herein, we report the obtaining of new hybrid molecules of amphetamine with different profens (amfens). The obtained amfens are characterized by their melting points, UV, 1H–, 13C–NMR, and HRMS spectra. A complete and detailed mass spectral analysis of the newly obtained derivatives of amphetamine with ibuprofen, flurbiprofen, ketoprofen, naproxen, and carprofen was performed. In vitro inhibition of albumin denaturation of each new compound was assessed, and they showed significant activity. The IC50 values of the obtained amphetamine-profen derivatives ranged from 92.81 to 159.87 µg/mL. This indicates that the new hybrids inherit the anti-inflammatory properties of profens. Using in silico method, the toxicity was also calculated. The obtained results are given in LD50 values. Depending on the route of administration, the amfens are less toxic compared to the standard amphetamine.

2-(2-Fluoro-[1,1′-biphenyl]-4-yl)-N-(4-methyl-2-oxo-2H-chromen-7-yl)propanamide

“…The 13 C NMR spectra confirm the structure of the newly discovered hybrid molecule 3. The two carbonyl carbons C=O are visible at 172.88 ppm and 160.46 ppm, respectively.…”

“…In prior research, we discovered that the fragmentation of profen derivatives is primarily caused by amide bond cleavage. The result is a profen cation that is resonance stable [13]. It is ion m/z 199 (C 14 H 12 F + ) in this specific instance, which is the flurbiprofen cation (Figure S5).…”

Novel Flurbiprofen Derivatives as Antioxidant and Anti-Inflammatory Agents: Synthesis, In Silico, and In Vitro Biological Evaluation

“…Cleavage of the C(O)-C bond (pathway 3) leads to a resonance-stable aromatic cation ( m / z 199) characteristic of flurbiprofen found in our previous studies ( Scheme 2 ) [ 19 ]. In ESI-MS conditions, the identical ion experiences the removal of a neutral HF molecule, a CH 3 radical, and a phenyl nucleus, resulting in the formation of ions with m/z values of 179, 184, and 105, correspondingly (as illustrated in Scheme 2 and depicted in Figures S17, S20, S23, S26 and S29 ).…”

“…In compound 4b, the methoxy group is situated in the meta position relative to the amide bond, whereas in 4c, it is located in the para position. Additionally, the dissimilarity between the two isomers is evident in the intensity of the m/z 199 and m/z 152 fragment ions, which exhibit greater intensity in the spectrum of 4b (see FiguresS20 and S23).Cleavage of the C(O)-C bond (pathway 3) leads to a resonance-stable aromatic cation (m/z 199) characteristic of flurbiprofen found in our previous studies (Scheme 2)[19]. In ESI-MS conditions, the identical ion experiences the removal of a neutral HF molecule,…”

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

“…Medicinal chemists have reported the synthesis and biological activities of flurbiprofen derivatives including, Manolov et al ., reported the synthesis, anti‐oxidant and anti‐inflammatory activities of novel amide derivatives with outstanding results [33] . Likewise, Momin et al ., reported the synthesis with α‐amylase inhibitory activity of flurbiprofen based oxadiazoles, [19] while Sajjad with his team members reported the synthesis and urease inhibition activity of novel derivatives with excellent results [18,34] .…”