Anti-Inflammatory, Analgesic and Antioxidant Potential of New (2S,3S)-2-(4-isopropylbenzyl)-2-methyl-4-nitro-3-phenylbutanals and Their Corresponding Carboxylic Acids through In Vitro, In Silico and In Vivo Studies

Abstract

In the current study, a series of new (2S,3S)-2-(4-isopropylbenzyl)-2-methyl-4-nitro-3-phenylbutanals (FM1-6) with their corresponding carboxylic acid analogues (FM7-12) has been synthesized. Initially, the aldehydic derivatives were isolated in the diastereomeric form, and the structures were confirmed with NMR, MS and elemental analysis. Based on the encouraging results in in vitro COX 1/2, 5-LOX and antioxidant assays, we oxidized the compounds and obtained the pure single (major) diastereomer for activities. Among all the compounds, FM4, FM10 and FM12 were the leading compounds based on their potent IC50 values. The IC50 values of compounds FM4, FM10 and FM12 were 0.74, 0.69 and 0.18 µM, respectively, in COX-2 assay. Similarly, the IC50 values of these three compounds were also dominant in COX-1 assay. In 5-LOX assay, the majority of our compounds were potent inhibitors of the enzyme. Based on the potency and safety profiles, FM10 and FM12 were subjected to the in vivo experiments. The compounds FM10 and FM12 were observed with encouraging results in in vivo analgesic and anti-inflammatory models. The molecular docking studies of the selected compounds show binding interactions in the minimized pocked of the target proteins. It is obvious from the overall results that FM10 and FM12 are potent analgesic and anti-inflammatory agents.

Biological Evaluation, Phytochemical Screening, and Fabrication of Indigofera linifolia Leaves Extract-Loaded Nanoparticles

“…Phytochemicals such as phenolics have been found in abundance in plants, and different health benefits such as antioxidant activity have been claimed by virtue of such rich phytochemical compositions [ 37 , 38 ]. Mahmood et al [ 39 ] also found that the antioxidant properties of natural resources were highly associated with their primary chemical content, such as polyphenols. Curcumin encapsulated by nano and pickering emulsion stabilized by chitosan-tripolyphosphate nanoparticles have been evaluated for their radical scavenging activity and higher results were recorded for the formulations as compared to free curcumin, which dictates the protective effect of the emulsion systems on the antioxidant activity of curcumin bioactive compounds [ 40 ].…”

Neuroprotective Effect of Natural Compounds in Paclitaxel-Induced Chronic Inflammatory Pain

“…Molecular research is primarily responsible for determining the expression of a wide variety of different types of inflammatory mediators and transcription factors. These molecular methods include the enzyme linked immunosorbent assay as well as the Western blot, both of which are utilized to evaluate the levels of endogenous marker expression [ 50 , 51 , 52 ]. The upregulation of inflammatory markers such as COX-2, TNF-a, and NF-kB, which are typically linked to chemotherapy-induced neuropathic pain, were also investigated as part of our research.…”

Isoprenaline and salbutamol inhibit pyroptosis and promote mitochondrial biogenesis in arthritic chondrocytes by downregulating β-arrestin and GRK2

“…Cartilage homogenates were made, centrifuged and serum was carefully collected by Pasteur pippete. CAT, POD, SOD, GSH were measured in the serum according to our previous protocol mentioned by Ul Hassan and Mahmood in their respective study (Ul Hassan et al, 2021 ; Mahmood et al, 2022 ). Briefly, rate of hydrolysis of H 2 O 2 was measured spectrophotometrically at 240 nm for measuring serum catalase.…”