Non-Complex Drug Substances

Keyword(s):  
2015 ◽  
Vol 407 (29) ◽  
pp. 8647-8659 ◽  
Author(s):  
Sarah Rogstad ◽  
Eric Pang ◽  
Cynthia Sommers ◽  
Meng Hu ◽  
Xiaohui Jiang ◽  
...  

Author(s):  
A. G. Zhukova ◽  
L. G. Gorokhova ◽  
A. S. Kazitskaya ◽  
T. K. Yadykina ◽  
N. N. Mikhailova ◽  
...  

Introduction. Fluorine compounds in small doses, but with prolonged exposure, cause various disorders in organs at the cellular and molecular levels. Activation of free-radical processes plays an important role in the damaging eff ect of fl uorides. Th erefore, one of the most eff ective ways to limit fl uorine-induced damage is to directly aff ect free-radical processes using herbal preparations with antioxidant properties.The aim of the study is to study the eff ect of a dihydroquercetin-based drug on the activity of free radical processes in brain tissue under subchronic exposure to sodium fl uoride (NaF).Materials and methods. Th e work was performed on white male laboratory rats weighing 200-250 g. Th e rats were divided into 3 groups: 1 — control; 2 — rats with chronic exposure to sodium fl uoride (NaF) for 9 weeks; 3 — rats receiving a NAF solution with simultaneous administration of a complex drug based on dihydroquercetin at a dose of 3 mg/kg in 1% starch gel for 3, 6 and 9 weeks. The activity of free radical oxidation and antioxidant defense enzymes — superoxide dismutase (SOD) and catalase-was determined in the cerebral cortex. Th e level of expression of hypoxia-induced transcription factor HIF — 1A and inducible forms of proteins HSP72 and HSP32 were determined in the cytosolic fraction of brain tissue.Results. In the early stages of subchronic fl uoride exposure (1-3 weeks), the expression of protective proteins HIF-1α, HSP72, HSP32 and catalase was shown in the rat cortex, as a result of which the activity of free-radical processes was maintained at the control level. An increase in the timing of fl uoride intake to 9 weeks led to a decrease in antioxidant protection and signifi cant activation of free radical oxidation in brain tissue. Daily administration of a complex drug with dihydroquercetin for 3, 6 and 9 weeks to rats with subchronic fl uoride exposure led to a decrease in the severity of pro- and antioxidant balance disorders in the cerebral cortex. At the same time, the greatest protective eff ect of dihydroquercetin with fl uoride exposure was manifested by the 9th week of its administration.Conclusions. When subchronic intake of fl uorides in the body, the drug based on dihydroquercetin has a neuroprotective eff ect, which is manifested by an increase in the activity of antioxidant enzymes of fr ee radical oxidation and catalase and the resistance of the cortex to induced fr ee radical oxidation.


2019 ◽  
Vol 18 (26) ◽  
pp. 2209-2229 ◽  
Author(s):  
Hai Pham-The ◽  
Miguel Á. Cabrera-Pérez ◽  
Nguyen-Hai Nam ◽  
Juan A. Castillo-Garit ◽  
Bakhtiyor Rasulev ◽  
...  

One of the main goals of in silico Caco-2 cell permeability models is to identify those drug substances with high intestinal absorption in human (HIA). For more than a decade, several in silico Caco-2 models have been made, applying a wide range of modeling techniques; nevertheless, their capacity for intestinal absorption extrapolation is still doubtful. There are three main problems related to the modest capacity of obtained models, including the existence of inter- and/or intra-laboratory variability of recollected data, the influence of the metabolism mechanism, and the inconsistent in vitro-in vivo correlation (IVIVC) of Caco-2 cell permeability. This review paper intends to sum up the recent advances and limitations of current modeling approaches, and revealed some possible solutions to improve the applicability of in silico Caco-2 permeability models for absorption property profiling, taking into account the above-mentioned issues.


2020 ◽  
Vol 13 ◽  
Author(s):  
Sara Cesarec ◽  
Jonathan A. Robson ◽  
Laurence S. Carroll ◽  
Eric O. Aboagye ◽  
Alan C. Spivey

Background: One of the challenges in positron emission tomography (PET) is labelling complex aliphatic molecules. Objective: To develop a method of metal-catalysed radiofluorination that is site-selective and works in moderate to good yields under facile conditions. Methods: We report here on the optimisation of an aliphatic C-H to C-18F bond transformation catalysed by a Mn(porphyrin) complex. Results: The successful oxidation of 11 aliphatic molecules including progesterone are reported. Radiochemical Incorporations (RCIs) up to 69% were achieved within 60 min without the need for pre-activation or specialist equipment. Conclusion: The method features mild conditions (60 °C) and promises to constitute a valuable approach to labelling of biomolecules and drug substances.


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