Comparative in-vitro anti-inflammatory, anticholinesterase and antidiabetic evaluation: computational and kinetic assessment of succinimides cyano-acetate derivatives

Pervaiz, Aini; Jan, Muhammad; Shah, Syed Muhammad Hassan; Khan, Ali; Zafar, Rehman; Ansari, Bushra; Shahid, Muhammad; Hussain, Fida; Khan, Mohammad Ijaz; Zeb, Anwar; Shah, Syed Muhammad Mukarram

doi:10.1080/07391102.2022.2069862

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…Best ligand receptor interactions were obtained that gave increased negative values. Among all, the best conformations were saved and visualized through Biovia Discovery Studio Visualizer (DSV), Ligplot software and Pymol 1.8 [39] …”

Section: Resultsmentioning

confidence: 99%

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Design, Synthesis, Molecular Docking, and Anti‐Inflammatory Potential of Amide Coupling Carboxylate Derivatives

Akbar,

Muhammad,

Jan

et al. 2024

ChemistrySelect

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Eight new amide‐based carboxylate derivatives were synthesized and evaluated for anti‐inflammatory potentials using in‐vitro, in‐vivo and in silico studies. In cyclooxygenase‐2 assay, maximum percent antagonist potential was exhibited by sodium 4‐((4‐fluorophenyl) amino)‐4‐oxobutanoate (93.91 %), bis ((4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoyl)oxy) zinc (93.04 %), and bis ((4‐((4‐bromo‐2‐fluorophenyl) amino)‐4‐oxobutanoyl)oxy)zincio (2‐bromopyridine) (92.64 %) with IC50 values of 1.65, 2.08, and 0.288 μM/ml respectively. Celecoxib demonstrated 98.60 % effect with an IC50 value of 0.041 μM/ml. In LOX assay, 4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoic acid (97.03 %), bis ((4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoyl)oxy)zinc (95.45 %), and (92.53 %) demonstrated maximum percent effect with IC50 values 3.48, 0.45, and 0.83 μM/ml respectively. The standard 5‐lipoxygenase inhibitor (montelukast) resulted from a 98.39 % inhibitory effect with an IC50 value of 0.194 μM/ml. In in‐vivo analysis, the potent tested compounds (5, 10, and, 20 mg/kg) significantly (p<0.001) reversed the induced edema by carrageenan. The standard drug aspirin displayed significant results (74–83 %). The standard drugs in these phlogestic agents displayed excellent results like cetirizine (67.9 %), celecoxib (81.61 %), icatibant (82.22 %) and nemesulide (87.17 %) at 5th h. The compounds displayed the inhibitory potential against targeted proteins. 4‐((4‐methoxy‐2‐nitrophenyl)amino)‐4‐oxobutanoic acid, 4‐((4‐fluorophenyl)amino)‐4‐oxobutanoic acid and sodium 4‐((4‐bromo‐2‐fluorophenyl)amino)‐4‐oxobutanoate shown excellent behavior by giving negative binding energies close of standard drugs montelukast (5F1A: −7.9 kcal/mol) and diclofenac (3O8Y: −8.5 Kcal/mol). The tested compounds were proven significant anti‐inflammatory potentials.

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Section: Resultsmentioning

confidence: 99%

“…Among all, the best conformations were saved and visualized through Biovia Discovery Studio Visualizer (DSV), Ligplot software and Pymol 1.8. [39]…”

Section: Possible Anti -Inflammatory Mechanismmentioning

confidence: 99%

Design, Synthesis, Molecular Docking, and Anti‐Inflammatory Potential of Amide Coupling Carboxylate Derivatives

Akbar,

Muhammad,

Jan

et al. 2024

ChemistrySelect

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“…The 5-LOX inhibitory experiments on H. digitata samples were carried out as per published protocol ( Pervaiz et al, 2022 ). Several concentrations of plant samples were made, with concentrations ranging from 31.25 to 1,000 μg/mL.…”

Section: Methodsmentioning

confidence: 99%

Phenolic phytochemistry, in vitro, in silico, in vivo, and mechanistic anti-inflammatory and antioxidant evaluations of Habenaria digitata

Almasoudi,

Saeed Jan,

Nahari

et al. 2024

Front. Pharmacol.

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Excessive and imbalance of free radicals within the body lead to inflammation. The objective of the current research work was to explore the anti-inflammatory and antioxidant potential of the isolated compounds from Habenaria digitata. In this study, the isolated phenolic compounds were investigated for in vitro and in vivo anti-inflammatory potential along with the antioxidant enzyme. The anti-inflammatory and antioxidant potential of the phenolic compounds was assayed via various enzymes like COX-1/2, 5-LOX and ABTS, DPPH, and H2O2 free radical enzyme inhibitory assay. These compounds were also explored for their in vivo antioxidant activity like examining SOD, CAT, GSH-Px, and MDA levels in the brain, heart, and liver. The anti-inflammatory potential was evaluated using the carrageenan-induced pleurisy model in mice. On the basis of initial screening of isolated compounds, the most potent compound was further evaluated for the anti-inflammatory mechanism. Furthermore, the molecular docking study was also performed for the potent compound. The phenolic compounds were isolated and identified by GC-MS/NMR analysis by comparing its spectra to the library spectra. The isolated phenolic compounds from H. digitata were 5-methylpyrimidine-24,4-diol (1), 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (2), 2-isopropyl-5-methylphenol (3), 3-methoxy-4-vinylphenol (4), and 2,6-dimethoxy-4-vinylphenol (5). In in vitro antioxidant assay, the most potent compound was compound 1 having IC50 values of 0.98, 0.90, and 5 μg/mL against ABTS, DPPH, and H2O2, respectively. Similarly, against COX1/2 and 5-LOX ,compound 1 was again the potent compound with IC50 values of 42.76, 10.70, and 7.40 μg/mL. Based on the in vitro results, compound 1 was further evaluated for in vivo antioxidant and anti-inflammatory potential. Findings of the study suggest that H. digitata contains active compounds with potential anti-inflammatory and antioxidant effects. These compounds could be screened as drug candidates for pharmaceutical research, targeting conditions associated with oxidative stress and inflammatory conditions in medicinal chemistry and support their ethnomedicinal use for inflammation and oxidative stress.

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“…This compound is reacted with N -benzylmaleimide to synthesize the targeted compound 3 . Previously, we explored various succinimide derivatives for their anti-diabetic potential [ 33 , 34 , 35 , 36 ]. The results of the previous studies are so much attractive that it is why we designed the current study.…”

Section: Introductionmentioning

confidence: 99%

Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches

et al. 2023

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Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonum aviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.

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Comparative in-vitro anti-inflammatory, anticholinesterase and antidiabetic evaluation: computational and kinetic assessment of succinimides cyano-acetate derivatives

Cited by 9 publications

References 44 publications

Design, Synthesis, Molecular Docking, and Anti‐Inflammatory Potential of Amide Coupling Carboxylate Derivatives

Design, Synthesis, Molecular Docking, and Anti‐Inflammatory Potential of Amide Coupling Carboxylate Derivatives

Phenolic phytochemistry, in vitro, in silico, in vivo, and mechanistic anti-inflammatory and antioxidant evaluations of Habenaria digitata

Exploration of Succinimide Derivative as a Multi-Target, Anti-Diabetic Agent: In Vitro and In Vivo Approaches

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