Determination of (4-(1,3-dioxo-1,3-dihydro-2H -isoindol- 2-yl)-N ′-[(4-ethoxyphenyl) methylidene] benzohydrazide, a novel anti-inflammatory agent, in biological fluids by UPLC-MS/MS: Assay development, validation and in vitro metabolic stability study

2017 ◽  
Vol 31 (10) ◽  
pp. e3981 ◽  
Author(s):  
Muzaffar Iqbal ◽  
Mashooq A. Bhat ◽  
Mohammad Raish ◽  
Essam Ezzeldin
Keyword(s):  
Biological Fluids ◽  
Stability Study ◽  
Metabolic Stability ◽  
Assay Development ◽  
Inflammatory Agent ◽  
Anti Inflammatory ◽  
Metabolic Stability Study

A highly efficient and sensitive LC-MS/MS method for the determination of afatinib in human plasma: application to a metabolic stability study

2016 ◽  
Vol 30 (8) ◽  
pp. 1248-1255 ◽  
Author(s):  
Adnan A. Kadi ◽  
Ali S. Abdelhameed ◽  
Hany W. Darwish ◽  
Mohamed W. Attwa ◽  
Nasser S. Al-Shakliah
Keyword(s):  
Human Plasma ◽  
Stability Study ◽  
Metabolic Stability ◽  
Highly Efficient ◽  
Metabolic Stability Study

Curcumin: Natural Antimicrobial and Anti Inflammatory Agent

2021 ◽  
pp. 1-8
Author(s):  
Pehlivanović Belma ◽  
Čaklovica Kenan ◽  
Lagumdžija Dina ◽  
Omerović Naida ◽  
Žiga Smajić Nermina ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Protein Denaturation ◽  
Dose Range ◽  
In Vitro Assays ◽  
Natural Antimicrobial ◽  
In Vivo Models ◽  
Vitro Assay ◽  
Inflammatory Agent ◽  
Anti Inflammatory

The pursuance of novel antimicrobial and anti-inflammatory agents has been expanding due to a significant need for more efficient pharmacotherapy of various infections and chronic diseases. During the last decade, pharmacokinetics, pharmacodynamics and pharmacological properties of curcumin have been extensively studied. The aim of the present study was to evaluate the antibacterial activity of curcumin against both Gram-positive and Gram-negative bacteria as well as its antifungal activity by using in vitro agar well diffusion assay. Moreover, the anti-inflammatory activity of curcumin was determined with in vitro assay of inhibition of protein denaturation. Results demonstrated wide antimicrobial activity of curcumin upon all of the test bacteria and fungi. The strongest activity of curcumin was observed at a concentration of 0.50 mg/ml against S. aureus, L. monocytogenes, E. coli, P. aeruginosa and C. albicans, resulting in a maximum zone of inhibition of 14.7 mm, 14.3 mm, 13.7 mm, 10.7 mm and 10.7 mm, respectively. Findings suggested that the antimicrobial activity of curcuminis dependent upon the concentrations. Furthermore, results demonstrated high effectiveness of curcumin compared to standard acetylsalicylic acid in inhibiting heat-induced protein denaturation, which activity is also depended upon the concentrations. The present study emphasises the potential application of curcumin as a natural antimicrobial and anti-inflammatory agent. However, findings of this study are restricted to in vitro assays and consideration should be given to conducting a study involving wider dose range test substances as well as including further research on in vivo models.

scholarly journals Construction of a novel quinoxaline as a new class of Nrf2 activator

2019 ◽  
Author(s):  
Murugesh Kandasamy ◽  
Kit-Kay Mak ◽  
Thangaraj Devadoss ◽  
Punniyakoti Veeraveedu Thanikachalam ◽  
Raghavendra Sakirolla ◽  
...  
Keyword(s):  
Docking Studies ◽  
Metabolic Stability ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
New Class ◽  
Ic50 Value ◽  
Kelch Domain ◽  
Anti Inflammatory ◽  
Nrf2 Activator

Abstract The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation provides cytoprotection against numerous inflammatory disorders. N-nicotinoylquinoxaline-2-carbohdyrazide (NQC) was designed by combining the important pharmacophoric features of bioactive compounds reported in the literature. NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using LPSEc induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using ELISA. The Nrf2 activity of the compound NQC was determined using ‘Keap1:Nrf2 Inhibitor Screening Assay Kit’. To obtain the insights on NQC’s activity on Nrf2, molecular docking studies were performed using Schrodinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes. NQC was found to be non-toxic until the dose of 50 µM on RAW 264.7 cells. The NQC showed potent anti-inflammatory effect in an in vitro model of Lipopolysaccharide (LPS) stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. The NQC dose-dependently down regulated the pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α) and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values 13.27 ± 2.37, 10.13 ± 0.58, 14.41 ± 1.83 and 15.23 ± 0.91 µM respectively. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 59.78 ± 6.73, 52.93 ± 7.81, 28.43 ± 8.13 minutes; microsomal intrinsic clearance values; 22.1 ± 4.31, 26.0 ± 5.17 and 47.13 ± 6.34 µL/min/mg protein; respectively. So, rat has comparable metabolic profile with human, thus, rat could be used for predicting the pharmacokinetics and metabolism of NQC in human. NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

scholarly journals Spectrofluorometric determination of nicardipine, nifedipine and isradipine in pharmaceutical preparations and biological fluids

2008 ◽  
Vol 6 (2) ◽  
pp. 222-228 ◽  
Author(s):  
Sheikha Al-Ghannam ◽  
Abeer Al-Olyan
Keyword(s):  
Fluorescence Intensity ◽  
Reaction Pathway ◽  
Biological Fluids ◽  
Sodium Dodecyl ◽  
Pharmaceutical Preparations ◽  
Reduction Reaction ◽  
Factors Affecting ◽  
Plasma And Urine Samples

AbstractA simple and highly sensitive spectrofluorometric method was developed for the determination of some 1,4-dihydropyridine compounds namely, nicardipine, nifedipine and isradipine in pharmaceutical preparations and biological fluids. The method is based on the reduction of nicardipine, nifedipine and isradipine with Zn/HCl and measuring the fluorescence intensity obtained (λem/λex) at 460/364, 450/393 and 446/360 nm, respectively. The factors affecting the development of the fluorophore and its stability were studied and optimized. The effect of some surfactants such as β-cyclodextrin (βCD), carboxymethylcelullose (CMC), sodium dodecyl sulphate (SDS) and triton X-100, on the fluorescence intensity was studied. The fluorescence intensity-concentration plots of nicardipine, nifedipine and isradipine were rectilinear over the ranges 0.4–6.0, 0.2–4.0 and 0.1–9.0 μg ml−1 with detection limits of 0.0028, 0.017 and 0.016 μg ml−1, respectively. The proposed method was successfully applied to commercial tablets containing the compounds; the percentage recovery agreed well with those obtained using the official methods. The method was further extended to the in vitro determination of the compounds in spiked human plasma and urine samples. A proposal of the reduction reaction pathway was postulated.

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