scholarly journals Identification of Bichalcones as Sirtuin Inhibitors by Virtual Screening and in Vitro Testing

2018 ◽  
Author(s):  
Berin Karaman ◽  
Zayan Alhalabi ◽  
Sören Swyter ◽  
Shetonde O. Mihigo ◽  
Kerstin Andrae-Marobela ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Histone Deacetylases ◽  
Metabolic Disorders ◽  
Biological Activities ◽  
In Vitro Assay ◽  
Sirtuin 1 ◽  
Class Iii ◽  
Vitro Assay ◽  
Pan African

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylases and have been linked to the pathogenesis of numerous diseases such as HIV, metabolic disorders, neurodegeneration and cancer. Docking of the virtual pan-African natural products library (p-ANAPL), followed by in vitro testing, resulted in the identification of two inhibitors of sirtuin 1, 2 and 3 (sirt1-3). Two bichalcones; rhuschalcone IV (8) and rhuschalcone I (9), previously isolated from the medicinal plant Rhus pyroides, were shown to be active in the in vitro assay, with rhuschalcone I showing the best activity against sirt1, having an IC50 = 40.8 µM. Based on the docking experiments, suggestions for improving the biological activities of the newly identified hit compounds have been provided.

scholarly journals Kinetic characterization of inhibitors of histone deacetylases (HDACs) and sirtuins

2019 ◽  
Author(s):  
Carlos Moreno-Yruela ◽  
Andreas Stahl Madsen ◽  
Christian A. Olsen
Keyword(s):  
Histone Deacetylases ◽  
Hdac Inhibitors ◽  
Kinetic Properties ◽  
Kinetic Characterization ◽  
Class Iii ◽  
Vitro Assay ◽  
Substrate Conversion ◽  
Fluorogenic Peptide Substrate

Abstract Histone deacetylase (HDAC) inhibitors are employed for the treatment of lymphoma and are under development against multiple other types of cancer and neurodegenerative diseases. Here, we describe a robust and uncomplicated in vitro assay for HDAC inhibitor kinetic profiling. Enzyme and fluorogenic peptide substrate are incubated together with a small amount of protease “assay developer”, which enables continuous recording of substrate conversion under steady-state conditions. Assay progression curves upon addition of an inhibitors at varying concentrations permit determination of kinetic constants and overall inhibitor potency. This assay helped provide new insight into the kinetic properties of known HDAC inhibitors as well as the kinetic characterization of both inhibitors and substrates of sirtuin enzymes, which are class III HDACs involved in metabolic control and oncogene regulation.

scholarly journals STUDI IN VITRO POTENSI ANTIOKSIDAN DAN AKTIFITAS ANTIDIABETES FRAKSI ETIL ASETAT BUAH PARIJOTO (Medinilla speciosa B.)

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Rissa Vifta ◽  
Wilantika Wilantika ◽  
Yustisia Dian Advistasari
Keyword(s):  
Ethyl Acetate ◽  
Biological Activities ◽  
Ethyl Acetate Fraction ◽  
In Vitro Assay ◽  
Antidiabetic Activity ◽  
Vitro Assay ◽  
Antioxidants Activity ◽  
Ic50 Value ◽  
Ic50 Values

ABSTRACT Parijoto fruit (Medinilla speciosa B) contains the flavonoid which is one of the phenolic groups compounnd. Flavonoids has biological activities as anti free radical and antionxidants. The aim of this research was to evaluate the potency of ethyl acetat fraction of M.speciosa B. Extract as an antioxidants and antidiabetic. Evaluation of antioxidants activity was carried out by in vitro assay using the ABTS method (2.2 azinobis (3-ethylbenzotiazolin) -6-sulfonic acid), while the antidiabetic assay was carried out using the Nelson-Somogyi method. Research begins with the process of determination, extraction, fravtionation and contiunued by examination of each variable. The parameters of antioxidants activity was determined by IC50 values, while antidiabetic activity was measured by percentage of decreasing of glucoce levels. The results of antioxidants activity showed that ethyl acetate fraction of M. Speciosa B. had antioxidants activity with an IC50 value of 4,246 ppm with a very strong category. In line with these results, ethyl acetate fraction of M. speciosa B. had reduced glucoce levels with an optimal decrease of 50.21% a concentration of 40 ppm.   ABSTRAK Buah Parijoto (Medinilla speciosa B.) mengandung senyawa aktif flavonoid yang merupakan salah satu golongan fenolik. Flavonoid memiliki aktifitas biologis sebagai antiradikal bebas dan antioksidan. Penelitian dilakukan dengan tujuan mengetahui kemampuan fraksi etil asetat M. speciosa B sebagai antioksidan dan antidiabetes. Pengujian aktifitas antioksidan dilakukan secara in vitro dengan metode ABTS (2,2 azinobis (3-etilbenzotiazolin)-6-asam sulfonat), sedangkan uji antidiabetes dilakukan menggunakan metode Nelson-Somogyi. Penelitian diawali dengan proses determinasi, ekstraksi, fraksinasi, dan dilanjutkan dengan pengujian pada masing-masing variabel. Parameter aktifitas antioksidan diwujudkan dengan nilai IC50, sedangkan aktiftas antidiabetes diukur dengan persen penurunan kadar glukosa. Hasil pengujian aktifitas antioksidan menunjukkan bahwa fraksi etil asetat memiliki aktifitas antioksidan dengan nilai IC50 sebesar 4.14±0.08 ppm dengan kategori sangat kuat. Sejalan dengan hasil tersebut, fraksi etil asetat Buah Parijoto (M. speciosa B.) memilili kemampuan dalam menurunkan kadar glukosa dengan penurunan secara optimal sebesar 50.21±0.47% pada konsentrasi 40 ppm.    

scholarly journals Sintesis dan Potensi Aktivitas Tabir Surya Senyawa Analog Kalkon Turunan 3’-Hidroksiasetofenon dan 4-Metoksibenzaldehid

2019 ◽  
Vol 10 (1) ◽  
pp. 1-12
Author(s):  
Ihsan Ikhtiarudin ◽  
Nesa Agistia ◽  
Tria Harlianti ◽  
Adel Zamri
Keyword(s):  
Microwave Irradiation ◽  
Active Ingredient ◽  
Biological Activities ◽  
In Vitro Assay ◽  
Vitro Assay ◽  
Assay Result ◽  
Microplate Reader ◽  
Sunscreen Product

Chalcone analogues have attracted the attention of researchers due to their various biological activities. In this study, a chalcone analogue, (E)-1-(3-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-on has been synthesized under microwave irradiation and its sunscreen activity has been evaluated by in vitro assay using 96-well microplate reader.  Based on the in vitro assay, at concentration of 100-500 µg/ml, the compound showed potential sunscreen activity with %Te value of 5.49 – 0.04 % (extra protection – sunblock), %Tp value of 0.51-0.05 % (sunblock) and SPF value of 18.20 – 32.91 (ultra protection). The assay result showed that the (E)-1-(3-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-on has a potency to be developed as active ingredient in sunscreen product.

In Vitro Assay of Platelet Adhesiveness with Washed and Tanned Human Red Cells

1968 ◽  
Vol 20 (03/04) ◽  
pp. 384-396 ◽  
Author(s):  
G Zbinden ◽  
S Tomlin
Keyword(s):  
Platelet Adhesion ◽  
Sodium Citrate ◽  
Blood Platelets ◽  
In Vitro Assay ◽  
Red Cells ◽  
Platelet Adhesiveness ◽  
Vitro Assay ◽  
In Vitro System ◽  
Human Red Cells

SummaryAn in vitro system is described in which adhesion of blood platelets to washed and tannic acid-treated red cells was assayed quantitatively by microscopic observation. ADP, epinephrine and TAME produced a reversible increase in platelet adhesiveness which was antagonized by AMP. With Evans blue, polyanetholsulfonate, phthalanilide NSC 38280, thrombin and heparin at concentrations above 1-4 u/ml the increase was irreversible. The ADP-induced increase in adhesiveness was inhibited by sodium citrate, EDTA, AMP, ATP and N-ethylmaleimide. EDTA, AMP and the SH-blocker N-ethylmaleimide also reduced spontaneous platelet adhesion to red cells. No significant effects were observed with adenosine, phenprocoumon, 5-HT, phthalanilide NSC 57155, various estrogens, progestogens and fatty acids, acetylsalicylic acid and similarly acting agents, hydroxylamine, glucose and KCN. The method may be useful for the screening of thrombogenic and antithrombotic properties of drugs.

Angiogenic Effect of Pravastatin Alone and with Sera from Healthy and Complicated Pregnancies Studied by in vitro Vasculogenesis/Angiogenesis Assay

2021 ◽  
pp. 1-9
Author(s):  
Anita Virtanen ◽  
Outi Huttala ◽  
Kati Tihtonen ◽  
Tarja Toimela ◽  
Tuula Heinonen ◽  
...  
Keyword(s):  
Direct Effect ◽  
Late Onset ◽  
Maternal Serum ◽  
In Vitro Assay ◽  
Serum Samples ◽  
Therapeutic Concentration ◽  
Tubule Formation ◽  
Vitro Assay ◽  
Angiogenesis Assay

<b><i>Objective:</i></b> To determine the direct effect of pravastatin on angiogenesis and to study the interaction between pravastatin and maternal sera from women with early- or late-onset pre-eclampsia (PE), intrauterine growth restriction, or healthy pregnancy. <b><i>Methods:</i></b> We collected 5 maternal serum samples from each group. The effect of pravastatin on angiogenesis was assessed with and without maternal sera by quantifying tubule formation in a human-based in vitro assay. Pravastatin was added at 20, 1,000, and 8,000 ng/mL concentrations. Concentrations of angiogenic and inflammatory biomarkers in serum and in test medium after supplementation of serum alone and with pravastatin (1,000 ng/mL) were measured. <b><i>Results:</i></b> Therapeutic concentration of pravastatin (20 ng/mL) did not have significant direct effect on angiogenesis, but the highest concentrations inhibited angiogenesis. Pravastatin did not change the levels of biomarkers in the test media. There were no changes in angiogenesis when therapeutic dose of pravastatin was added with maternal sera, but there was a trend to wide individual variation towards enhanced angiogenesis, particularly in the early-onset PE group. <b><i>Conclusions:</i></b> At therapeutic concentration, pravastatin alone or with maternal sera has no significant effect on angiogenesis, but at high concentrations the effect seems to be anti-angiogenic estimated by in vitro assay.

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