Identification of the first “two digit nano-molar” inhibitors of the human glyoxalase-I enzyme as potential anticancer agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Qosay A. Al-Balas ◽  
Mahmoud A. Al-Sha'er ◽  
Mohammad A. Hassan ◽  
Esra’a Al zu’bi
Keyword(s):  
Anticancer Agents ◽  
Essential Feature ◽  
In Vitro Assay ◽  
Glyoxalase I ◽  
Vitro Assay ◽  
Molar Activity ◽  
Competitive Inhibitors ◽  
Modeling Techniques ◽  
Catechol Moiety

Background: Glyoxalase-I (Glo-I) enzyme is recognized as an indispensable druggable target in cancer treatment. Its inhibition will lead to the accumulation of toxic aldehyde metabolites and cell death. Paramount efforts were spent to discover potential competitive inhibitors to eradicate cancer. Objective: Based on our previously work on this target for discovering potent inhibitors of this enzyme, herein, we address the discovery of the most potent Glo-I inhibitors reported in literature with two digits nano-molar activity. Methods: Molecular docking and in vitro assay were performed to discover these inhibitors and explore the active site's binding pattern. A detailed SAR scheme was generated, which identifies the significant functionalities responsible for the observed activity. Results: Compound 1 with an IC50 of 16.5 nM exhibited the highest activity, catechol moiety as an essential zinc chelating functionality. It has been shown by using molecular modeling techniques that the catechol moiety is responsible for the chelation zinc atom at the active site, an essential feature for enzyme inhibition. Conclusion: Catechol derivatives are successful zinc chelators in the Glo-I enzyme while showing exceptional activity against the enzyme to the nanomolar level.

ChemInform Abstract: 1-Aryl-3-(2-chloroethyl)ureas: Synthesis and in vitro Assay as Potential Anticancer Agents.

ChemInform ◽  
1988 ◽  
Vol 19 (31) ◽  
Author(s):  
R. C. GAUDREAULT ◽  
J. LACROIX ◽  
M. PAGE ◽  
L. P. JOLY
Keyword(s):  
Anticancer Agents ◽  
In Vitro Assay ◽  
Vitro Assay

1-Aryl-3-(2-chloroethyl) Ureas: Synthesis and In Vitro Assay as Potential Anticancer Agents

1988 ◽  
Vol 77 (2) ◽  
pp. 185-187 ◽  
Author(s):  
R.C. Gaudreault ◽  
J. Lacroix ◽  
M. Pagé ◽  
L.P. Joly
Keyword(s):  
Anticancer Agents ◽  
In Vitro Assay ◽  
Vitro Assay

Aromatase (CYP19) inhibition by biflavonoids obtained from the branches of Garcinia gardneriana (Clusiaceae)

2019 ◽  
Vol 74 (9-10) ◽  
pp. 279-282 ◽  
Author(s):  
Angelica Maria Recalde-Gil ◽  
Luiz Klein-Júnior ◽  
Juliana Salton ◽  
Sérgio Bordignon ◽  
Valdir Cechinel-Filho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Aromatase Inhibitors ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
In Vitro Assay ◽  
Aromatase Activity ◽  
Vitro Assay

Abstract Overexpression of aromatase in breast cancer cells may substantially influence its progression and maintenance. In this sense, the inhibition of aromatase is a key target for the treatment of breast cancer in postmenopausal women. Although several flavonoids had already demonstrated the capacity of inhibiting aromatase activity, the role of biflavonoids as aromatase inhibitors is poorly studied. In this work, the biflavonoids isolated from Garcinia gardneriana, morelloflavone (1), Gb-2a (2) and Gb-2a-7-O-glucose (3) were submitted to in vitro assay to evaluate the aromatase modulatory effect. As results, it was demonstrated that all biflavonoids were able to inhibit the enzyme, with IC50 values ranging from 1.35 to 7.67 μM. This demonstrates that biflavonoids are an important source of scaffolds for the development of new aromatase inhibitors, focusing on the development of new anticancer agents.

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.

In Vitro Assay for Single-cell Characterization of Impaired Deformability in Red Blood Cells under Recurrent Episodes of Hypoxia

Lab on a Chip ◽  
2021 ◽  
Author(s):  
YUHAO QIANG ◽  
Jia Liu ◽  
Ming Dao ◽  
E Du
Keyword(s):  
Shear Stress ◽  
Red Blood Cells ◽  
Single Cell ◽  
Blood Cells ◽  
Blood Circulation ◽  
In Vitro Assay ◽  
Vitro Assay ◽  
Cyclic Shear

Red blood cells (RBCs) are subjected to recurrent changes in shear stress and oxygen tension during blood circulation. The cyclic shear stress has been identified as an important factor that...

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