Vanishing Bile Duct Syndrome

Hamed, Ahmed; Hamed, Amira; Hamed, Nouran; Taha, Omar

doi:10.14309/00000434-201810001-01345

Cited by 4 publications

(5 citation statements)

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“…In the previously published studies, heterocyclic modification at the keto‐enol moiety of curcumin has been proven to be an important pharmacophore playing a pivotal role in various biological activities including antioxidant, anti‐Alzheimer's, anti‐androgenic and cytotoxicity. According to the literature, an appropriate modification at the keto‐enol region could cause enhanced potency . In this work, design, synthesis and evaluation of few semisynthetic curcumin analogues for cytotoxic activity against HNSCC cells are reported.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

et al. 2017

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Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anticancer activity against various types of cancers and high-safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27; however, these compounds did not show any activity on pSTAT3 phosphorylation at IC 50 concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3. K E Y W O R D Sclick chemistry curcumin analogue, curcumin, head and neck squamous cell carcinoma, pyrazole analogue Curcumin, a natural polyphenol which is used as a food colourant, and herbal medicine in Asia. Curcumin has received a lot of attention recently due to its high-safety profile and efficacy in treating various diseases.[1-3] Potential anticancer activities associated with curcumin make it a promising therapeutic agent. Apart from anticancer activity, it has shown antioxidant, anti-inflammatory, chemopreventive, chemotherapeutic, antimicrobial and antifungal activities. Curcumin (Figure 1) is being vigorously studied for its effect against breast cancer, prostate cancer, liver cancer, ovarian cancer and cervical cancer.[4] It demonstrated cytotoxic effects against cancer cell lines and cytoprotective effects on non-cancer cells. One of the important aspects of curcumin is its high-safety profile of up to 12 g per day oral administration.[5]Nevertheless, there are a number of challenges, low aqueous solubility, poor absorption and rapid metabolism that limits its therapeutic efficacy.[6] Curcumin can exist as a tautomeric mixture of keto and enol forms in solutions, and the enol form was found to be responsible for the rapid degradation of the curcumin. Chakraborti et al., [7] found that the stability of curcumin was improved when the central diketone moiety of the curcumin was replaced by isooxazole and pyrazole groups. Structural modifications of curcumin were proven to be a meaningful approach to discover analogues with enhanced properties. [8][9][10][11][12] Conjugates of curcumin with β-and γ-cyclodextrin, liposomal and loaded nanoparticles and nanoemulsion are some of the lipid-based colloidal system that has been employed to enhance water solubility and improving its bioavailability.[13] Recent work supports the

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Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

et al. 2017

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“…Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a yellow bioactive pigment is the major component of Turmeric. Curcumin shows some biological activities exhibiting anti-inflammatory [1–5], antifungal, anticarcinogenic, antibacterial [6], antiprotozoal wound healing, antispasmodic, anticoagulant, antitumor and hepatoprotective activities [7–10]. Antioxidant and wound-healing gives by curcumin, its anticancer and anti-viral attributes, its effect on lymphocytes, platlet aggregation, detoxification mechanism.…”

Section: Introductionmentioning

confidence: 99%

Medicinal Plant Using Ground State Stabilization of Natural Antioxidant Curcumin by Keto-Enol Tautomerisation

Manimaran¹,

Sambathkumar

Gayathri³

et al. 2018

Nat. Prod. Bioprospect.

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Curcumin is a medicinal agent that exhibits anti-cancer properties and bioactive pigment in Turmeric has a huge therapeutic value. It has a keto-enol moiety that gives rise to many of its chemical properties. A recent study has shown that keto-enol tautomerisation at this moiety is implicated the effect of curcumin. The tautomerisation of curcumin in methanol, acetone and acetonitrile are used in nuclear magnetic resonance (1H, 13C) spectroscopy. It was characterized using UV, IR and Raman spectral values. The molecular electrostatic potential surface of the Curcumin has been visualized in electropositive potential in the region of the CH3+ group and most electronegative potential in the two oxygen atom has very strong binding group. In the following, the modality of structural and thermo dynamical parameters, electrophilicity (ω), chemical potential (μ), chemical hardness (η) and electronic charge transfer confirms the local reactivity. The rate constant of tautomerisation of curcumin shows strong temperature dependence. Molecular electrostatic potential and Temperature dependence of various thermodynamic properties like is increase with increase in temperature for monomer and dimer of various electrical fields.

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“…Health-related quality of life was measured by the 12-Item Short-Form (SF-12) health survey physical component summary (PCS) and mental component summary (MCS) scales, the EuroQol 5-Dimension 5-Level (EQ-5D-5L) score and EQ-5D visual analog scale score . Patient-reported Pompe disease symptoms were assessed with the Rasch-built Pompe-Specific Activity Scale (R-PAct), Patient Global Impression of Change (PGIC) scale, Pompe Disease Symptom Scale (PDSS), and Pompe Disease Impact Scale (PDIS) …”

Section: Methodsmentioning

confidence: 99%

Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks

et al. 2023

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ImportanceIn the previously reported Comparative Enzyme Replacement Trial With neoGAA Versus rhGAA (COMET) trial, avalglucosidase alfa treatment for 49 weeks showed clinically meaningful improvements in upright forced vital capacity (FVC) percent predicted and 6-minute walk test (6MWT) compared with alglucosidase alfa.ObjectiveTo report avalglucosidase alfa treatment outcomes during the COMET trial extension.Design, Setting, and ParticipantsThis phase 3 double-blind randomized clinical trial with crossover in the extension period enrolled patients 3 years and older with previously untreated late-onset Pompe disease (LOPD) between November 2, 2016, and February 10, 2021, with primary analysis after 49 weeks. Patients were treated at 55 referral centers in 20 countries. Efficacy outcomes were assessed at 97 weeks and safety outcomes to last follow-up, with data cutoff at February 10, 2021. Data were analyzed from May to June 2021.InterventionsRandom assignment (1:1) to receive 20 mg/kg of avalglucosidase alfa or alglucosidase alfa by intravenous infusion every other week for 49 weeks; thereafter, all patients received 20 mg/kg of avalglucosidase alfa every other week.Main Outcomes and MeasuresThe primary outcome was the least squares (LS) mean change from baseline in FVC percent predicted. Secondary outcomes included the LS mean change from baseline in 6MWT, muscle strength, motor function, quality of life, and disease biomarkers. Safety and tolerability were also assessed.ResultsOf 100 participants from the double-blind treatment period, 95 entered the extension period. Of these, 51 (54%) were men, and the mean (range) age was 48.3 (10-79) years. At the start of this study, mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 97, LS mean (SE) FVC percent predicted increased by 2.65 (1.05) for those who continued avalglucosidase alfa and 0.36 (1.12) for those who switched to avalglucosidase alfa. The LS mean (SE) 6MWT distance increased by 18.60 (12.01) m and 4.56 (12.44) m, respectively. For participants who switched to avalglucosidase alfa, FVC percent predicted remained stable (LS mean [SE] change from week 49 to 97, 0.09 [0.88]) and 6MWT distance improved (LS mean [SE] change from week 49 to 97, 5.33 [10.81] m). Potentially treatment-related adverse events were reported in 29 patients (56.9%) who continued avalglucosidase alfa and in 25 patients (56.8%) who switched.Conclusions and RelevanceIn this randomized clinical trial extension, maintenance of positive clinical outcomes was demonstrated for patients continuing avalglucosidase alfa treatment and, to a lesser extent, patients who switched from alglucosidase alfa. No new safety concerns were observed.Trial RegistrationClinicalTrials.gov Identifier: NCT02782741

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Vanishing Bile Duct Syndrome

Cited by 4 publications

References 0 publications

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Medicinal Plant Using Ground State Stabilization of Natural Antioxidant Curcumin by Keto-Enol Tautomerisation

Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks

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