Structural optimization of adaptaquin,a HIF prolyl hydroxylase inhibitor

Russian Chemical Bulletin - The structural optimization of adaptaquin, viz., 7-(4-chlorophenyl)[(3-hydroxypyridin-2-yl)amino]methylquinolin-8-ol, a HIF (hypoxia inducible factor) prolyl hydroxylase...     

Antioxidant and antihypoxic properties of neuroprotective drugs

Russian Chemical Bulletin - The screening of the library containing 320 drugs and biologically active compounds was carried out. The library was created for testing potent agents on Rett syndrome...     

Optimal Disturbances of Bistable Time-Delay Systems Modeling Virus Infections

For bistable time-delay dynamical systems modeling the dynamics of viral infections and the virusinduced immune response, an efficient approach is proposed for constructing optimal disturbances of steady states with a high viral load that transfer the system to a state with a low viral load. Functions approximating the behavior of drugs within the framework of well-known pharmacokinetic models are used as basis functions. Optimal disturbances are sought in the W ₂ ¹ norm. It is shown that optimal disturbances found in this norm are superior to those found in the L₂ norm as applied to the development of adequate therapeutic strategies.     

HIF2 ODD-luciferase reporter: the most sensitive assay for HIF prolyl hydroxylase inhibitors

Russian Chemical Bulletin - Reporters expressing fusion proteins of HIF2 and HIF3 C-terminal oxygen degradable domain (ODD) with the firefly luciferase, HIF2 ODD-luc and HIF3 ODD-luc, were...     

Antihypoxic activity of adaptaquin enantiomers

Russian Chemical Bulletin - Adaptaquin, 7-{(4-chlorophenyl)[(3-hydroxypyridin-2-yl)amino]methyl}quinolin-8-ol (1), was identified in our earlier study as a hypoxia-inducible factor (HIF) prolyl...     

Metal Ions as Activators of Hypoxia Inducible Factor

Activation of antihypoxic program under the action of a number of transition and heavy metals has been studied using cell-based HIF1 ODD-luc and HRE-luc reporters. It has been demonstrated that Au³⁺, Pb²⁺, Sn²⁺, Hg²⁺ are weak HIF1 ODD-luc activators, likely reflecting their weak competition for the ironbinding site in the active center of HIF prolyl hydroxylase. Metals capable of replacing iron–Mn²⁺, Zn²⁺, Cu²⁺ и Ni²⁺–activate at high submillimolar concentrations, which indicates low permeability of the cell membrane for transition metals. The highest activation is observed for Co²⁺ and Cd²⁺, however, Cd²⁺ is highly toxic even at 10 μM, in contrast to Co²⁺, which activates both reporters without toxicity signs up to 25 μM for 24 h. A significant activation by Co²⁺ is observed already in low micromolar range of concentrations, which can be recommended for use in hypoxia mimicking.     

Transport and toxicity of 5-fluorouracil,doxorubicin, and cyclophosphamide in in vitro placental barrier model based on BeWo b30 cells

An in vitro placental barrier model based on human choriocarcinoma BeWo b30 cell line was considered as a method of preclinical study of the transport and toxicity of antitumor agents and other organic compounds. Low permeabilities were found for 5-fluorouracil as an example of hydrophilic compound and for doxorubicin as an example of a lipophilic compound with a high degree of binding to proteins and DNA and a high permeability was found for cyclophosphamide as an example of lipophilic compound with a low degree of binding to proteins. Using impedance spectrometry and cell viability assessment via reduction of resazurin to resorufin, a pronounced cytotoxic effect of doxorubicin and good tolerance of 5-fluorouracil and cyclophosphamide by the cells were shown for drug concentrations equal to the maximum concentrations in the patients’ blood during the treatment of breast cancer.

     

Computation of Optimal Disturbances for Delay Systems

Computational Mathematics and Mathematical Physics - Novel fast algorithms for computing the maximum amplification of the norm of solution and optimal disturbances for delay systems are proposed...