Synthesis and Investigation of Heterocyclic Systems as Pharmacological Agents with Conformational Study and Surface Activity

2021 ◽  
pp. 130597
Author(s):  
Refat El-Sayed ◽  
Ismail Althagafi ◽  
Moataz Morada ◽  
Salah M. El-Bahy ◽  
Nashwa El-Metwaly
1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.


2019 ◽  
Vol 4 (6) ◽  
pp. 377-383
Author(s):  
M. V. Kuzmenko ◽  
◽  
L. M. Gunina ◽  
O. V. Nosach ◽  
R. V. Golovashchenko ◽  
...  

2020 ◽  
Vol 5 (5) ◽  
pp. 386-393
Author(s):  
L. M. Gunina ◽  
◽  
Kazys Mylashyus ◽  
Voitenko V. L. ◽  
◽  
...  

Under high-intensity loads, the athlete's bodies take place a number of biochemical reactions and physiological processes that can lead to hyperbilirubinemia. The factors that can initiate the onset of this phenomenon include the syndrome of micro-damage muscle, violation of the integrity of erythrocyte membranes, decreased blood pH, malnutrition and increase oxygen demand of the body. Degree of expression of manifestations of physiological bilirubinemia depends on the level of adaptation of the athlete to the physical activities offered. Hyperbilirubinemia in athletes can be one of the components of the deterioration of the functional state, forming the symptoms of endogenous intoxication. The relevance of this problem in sport lies in the relatively low detection rate of hyperbilirubinemia due to the lack of regular screening studies. However, in drawing up a plan of nutritional- metabolic support for training and competitive activity and recovery measures, must not only the individual reaction of the athlete body to physical activity, but also the severity of shifts in the indicators of bilirubin metabolism and their ratio. The article describes the reasons for the increase in bilirubin levels, which can be caused by both the effect of physical activity and by the presence of pathological processes in athletes. The factors influencing the blood serum’s bilirubin content are also highlighted, which include the state of erythrocyte cell membranes and the rate of hemoglobin destruction, the functional state of the liver, the specifics of physical loads and the use of ergogenic pharmacological agents by athletes. Particular accent has been placed on the illumination of hereditary hyperbilirubinemias, which may have been detected at the stage of selection of athletes. The most common phenomenon is Gilbert's syndrome, which occurs in 2-5% of cases in the general population, is characterized in the clinic by a benign flow and is manifested by episodes of jaundice and an increase in total bilirubin content to moderate values due to indirect. The frequency of detection of hyperbilirubinemias in the population of athletes is 4.68%, among which Gilbert's disease accounts for almost half (48.7%). Conclusion. The work highlighted the pathogenesis and diagnostic algorithm of Gilbert's disease, and also emphasized that its drug prevention and correction in athletes to maintain functional and physical fitness should be carried out taking into account anti-doping rules, which requires upon diagnosis timely receipt of a therapeutic exclusion


Author(s):  
Sirisha Kalam ◽  
Sai Krishn G ◽  
Kumara Swamy D ◽  
Sai Santhoshi K ◽  
Durga Prasad K

Pharmacological agents that kills parasites are essential drugs in some tropical countries. In this study, a series of 2-amino substituted 4-phenyl thiazole derivatives (4a-e) have been synthesized by the conventional method. The thiazole derivatives were synthesized by three steps. The obtained five derivatives were purified by recrystallization using methanol as a solvent or column chromatography. They were characterized by melting point, TLC, FTIR, 1H NMR and MASS spectral data. Compounds 4a-e were evaluated in silico by using different software’s (Lipinski’s Rule of 5, OSIRIS molecular property explorer, Molsoft molecular property explorer, and PASS & docking studies). These compounds were then evaluated for their possible anthelmintic activity against Indian adult earth worms (Pherituma postuma). All the compounds displayed significant anthelmintic activity. Compound 4c and 4e were more potent compounds when compared with the standard drug (mebendazole). Molecular docking studies guided and proved the biological activity against beta tubulin protein (1OJ0). In conclusions, these new molecules have promising potential as anthelmintic for treatment of parasites.   


2020 ◽  
Vol 26 (18) ◽  
pp. 2096-2101
Author(s):  
Giuseppe Manfroni ◽  
Francesco Ragonese ◽  
Lorenzo Monarca ◽  
Andrea Astolfi ◽  
Loretta Mancinelli ◽  
...  

The human intermediate conductance calcium-activated potassium channel, KCa3.1, is involved in several pathophysiological conditions playing a critical role in cell secretory machinery and calcium signalling. The recent cryo-EM analysis provides new insights for understanding the modulation by both endogenous and pharmacological agents. A typical feature of this channel is the low open probability in saturating calcium concentrations and its modulation by potassium channel openers (KCOs), such as benzo imidazolone 1-EBIO, without changing calcium-dependent activation. In this paper, we proposed a model of KCOs action in the modulation of channel activity. The KCa3.1 channel has a very rich pharmacological profile with several classes of molecules that selectively interact with different binding sites of the channel. Among them, benzo imidazolones can be openers (positive modulators such as 1-EBIO, DC-EBIO) or blockers (negative modulators such as NS1619). Through computation modelling techniques, we identified the 1,4-benzothiazin-3-one as a promising scaffold to develop new KCa3.1 channel modulators. Further studies are needed to explore the potential use of 1-4 benzothiazine- 3-one in KCa3.1 modulation and its pharmacological application.


2019 ◽  
Vol 23 (2) ◽  
pp. 205-213
Author(s):  
Dorra Kanzari-Mnallah ◽  
Med L. Efrit ◽  
Jiří Pavlíček ◽  
Frédéric Vellieux ◽  
Habib Boughzala ◽  
...  

Thioxo, Oxo and Seleno diastereomeric cyclophosphamides containing 1,3,2- dioxaphosphorinane are prepared by a one-step chemical reaction. Their structural determination is carried out by means of Nuclear Magnetic Resonance NMR (31P, 1 H, 13C) and High-Resolution Mass Spectroscopy (HRMS). The conformational study of diastereomeric products is described. Density Functional Theory (DFT) calculations allowed the identification of preferred conformations. Experimental and calculated 31P, 13C, 1H NMR chemical shifts are compared. The molecular structure of the 2-Benzylamino-5-methyl-5- propyl-2-oxo-1,3,2-dioxaphosphorinane (3d) has been determined by means of crystal Xray diffraction methods.


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