Synthesis, molecular docking, and biological activities of new cyanopyridine derivatives containing phenylurea.

A new class of cyanopyridine derivatives (10a-e and 11a-e) containing the phenylurea unit was synthesized and tested against some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly). The new cyanopyridine derivatives showed Ki values in the range of 40.73 ± 6.54 to 87.05 ± 16.98 µM against AChE, 29.17 ± 4.88 to 124.03 ± 22.43 µM against BChE, and 3.66 ± 0.93 to 26.33 ± 5.05 µM against α-Gly. These inhibition effects were compared with standard enzyme inhibitors like tacrine (for AChE and BChE) and acarbose (for α-Gly). Also, these cyanopyridine derivatives with the best inhibition score were docked into the active site of the indicated metabolic enzymes. Finally, molecular docking calculations were made to compare the biological activities of the compounds against AChE (-8.81 kcal/mol for molecule 11d), BChE (-3.52 kcal/mol for molecule 11d), and α-Gly (-2.98 kcal/mol for molecule 11a). After molecular docking calculations, the ADME/T analysis was performed to examine the future drug use properties of the new cyanopyridine derivatives containing phenylurea.

Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives.

Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC50 values of 86-168 µM demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (∼6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1×103 M-1 -2.3×104 M-1 . The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.

Surface characterization and electroanalytical applications of the newly developed copper(II)-selective potentiometric sensor.

In this work, we developed a new copper(II)-selective potentiometric sensor and investigated its surface with scanning electron microscopy (SEM). Besides the surface images of the sensors conditioned in copper(II) solutions, energy-dispersive X-ray (EDX) and mapping studies were carried out. According to the results obtained, it was determined that copper(II) ions adhered to the porous areas on the sensor surface, and that Cu2+ ions showed a wide distribution on the sensor surface in mapping studies. The new sensor had a Nernstian response of 29.3 ± 0.5 mV/decade in the concentration range of 1.0 × 10-1-1.0 × 10-5 M and a low detection limit of 8.56 × 10-6 M. The proposed sensor had fast response time (< 10 s), wide pH working range (5.0-10.0), good repeatability and stability. Finally, the sensor performed the determination of copper(II) ions in various water samples with very high recoveries (96.0-102.0%).

Applications of Potentiometric Sensors for the Determination of Drug Molecules in Biological Samples.

Potentiometry is extensively studied by researchers as one of the electrochemical methods due to its multiple advantages. Until today, thousands of potentiometric sensors have been developed and applied successfully in many fields such as medicine, environmental monitoring, agriculture, industry and pharmaceutical sciences. Clinical drug analyses and determination of drugs in biological samples are highly important from a medical point of view. These analyses are carried out using various analytical devices including potentiometric sensors. These potentiometric sensors are superior to other devices in terms of several performance parameters, and thus present a good alternative for researchers. Using potentiometric sensors, very successful results in the identification of drug molecules in body fluids have been obtained and reported in the literature up to now. In this study, we review potentiometry-based sensors developed for the determination of drug molecules in various biological samples such as blood serum and urine, and touch upon their performance features in these applications.

Potentiometric urea biosensors.

Excess nitrogen in the body is converted to urea in the liver, and urea is disposed as a waste product in urine. Urea concentration can change in body fluids such as blood due to the presence of certain disorders. Therefore, the determination of urea is of high importance in various areas including medical diagnosis, as well as food quality control and environmental monitoring. Potentiometric sensors have certain advantages over their alternatives, such as rapidity, portability, cost effectiveness, high sensitivity, easy operation and simple apparatus. Potentiometric urea biosensors based on enzyme urease have been developed using various materials including nanoparticles and films, and also using different methodologies. In this review, we covered potentiometric urea biosensors reported in the literature, and touched upon their certain structure characteristics and performance parameters including detection limit, working concentration range, response time and lifetime, all of which are of practical importance. Each potentiometric urea biosensor has its own advantages and drawbacks, thus the selection of appropriate method depends on the sample to be analyzed, its urea concentration range and other requirements of the particular application. Further research is needed in order to optimize the performance of these devices and to broaden their applicability.

Application of Potentiometric Sensors in Real Samples.

Potentiometry is one of the most important electrochemical methods and potentiometric based sensors have been extensively studied by researchers for many years. The fact that potentiometric sensors have several advantages over other analytical devices is another reason for intensive research on the topic. In this area, hundreds of different sensors have been developed till today and introduced into the literature. The successful use of the developed sensors, particularly in real sample analysis, has made potentiometric sensors the center of attention. In this review, we highlight the studies which have been successfully applied to the developed drug samples and also to many real samples, with high recovery rates.