Inverse relationship between hSHBG affinity for testosterone and hSHBG concentration revealed by surface plasmon resonance

cited By 4International audienceA wide range of human sex hormone-binding globulin (hSHBG) affinity constants for testosterone (KAₕSHBG) has been reported in literature. To bring new insight on the KAₕSHBG value, we implemented a study of the molecular interactions occurring between testosterone and its plasma transport proteins by using surface plasmon resonance. The immobilization on the sensorchip of a testosterone derivative was performed by an oligoethylene glycol linker. For different plasmas with hSHBG concentrations, an assessment of the KAₕSHBG was obtained from a set of sensorgrams and curve-fitting these data. We observed that KAₕSHBG decreased, from at least two decades, when the plasma hSHBG concentration increased from 4.4 to 680 nmol/L. Our study shows a wide biological variability of KAₕSHBG that is related to the hSHBG concentration. These unexpected results may have a physiological significance and question the validity of current methods that are recommended for calculating free testosterone concentrations to evaluate androgen disorders in humans. © 2014 Elsevier Ireland Ltd

Synthesis of specific inhibitors of Haspin for potential cancer treatment.

International audienc

Synthesis of specific inhibitors of Haspin for potential cancer treatment.

International audienc

Synthesis, biological evaluation and binding mode of new CLK1/DYRK1A inhibitors presenting a pyrido[3,4-g]quinazoline moiety.

International audienc

QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor

Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and para-quinonic indeno[1,2-b]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4w with identical IC50 values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-b]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them (N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit CK2 with an IC50 value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM