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1.
Biomolecules ; 14(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38397418

RESUMO

Cold atmospheric plasma has become a widespread tool in bacterial decontamination, harnessing reactive oxygen and nitrogen species to neutralize bacteria on surfaces and in the air. This technology is often employed in healthcare, food processing, water treatment, etc. One of the most energy-efficient and universal methods for creating cold atmospheric plasma is the initiation of a piezoelectric direct discharge. The article presents a study of the bactericidal effect of piezoelectric direct discharge plasma generated using the multifunctional source "CAPKO". This device allows for the modification of the method of plasma generation "on the fly" by replacing a unit (cap) on the working device. The results of the generation of reactive oxygen and nitrogen species in a buffer solution in the modes of direct discharge in air and a plasma jet with an argon flow are presented. The bactericidal effect of these types of plasma against the bacteria E. coli BL21 (DE3) was studied. The issues of scaling the treatment technique are considered.


Assuntos
Escherichia coli , Gases em Plasma , Descontaminação/métodos , Oxigênio/farmacologia , Antibacterianos/farmacologia , Gases em Plasma/farmacologia , Bactérias , Nitrogênio
2.
Curr Drug Discov Technol ; 19(1): e010921191770, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33655836

RESUMO

BACKGROUND: Despite the introduction of direct oral anticoagulants, the search for new oral anticoagulants remains an urgent task. OBJECTIVE: By using docking and scoring, based on physical methods, simple chemical rules, methods of synthesis, and activity measurement, develop new low-molecular-weight inhibitors of factor Xa, which are potential anticoagulants. METHODS: The development of leads was based on chemical synthesis and structure-based drug design methods. The basic idea was to combine the two approaches: one based on predictive modeling and the other based on the experimental data. RESULTS: In this study, we developed some nanomolar leads. Further chemical modification improved the inhibition constant by more than one order. DISCUSSION: The method proposed in this paper, as well as other methods, includes virtual screening, chemical synthesis, and activity measurement. However, the most time-consuming process in this method (chemical synthesis) was simplified, and the cost was reduced to the extent that was allowed; a very simple chemical reaction was chosen, i.e., the formation of an amide bond. CONCLUSION: In this work, we demonstrated how using simple chemical rules based on the structurebased drug design, substances with a nanomolar concentration of activity can be developed.


Assuntos
Anticoagulantes , Inibidores do Fator Xa , Amidas , Anticoagulantes/química , Anticoagulantes/farmacologia , Desenho de Fármacos
3.
Materials (Basel) ; 14(21)2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34772007

RESUMO

In this article, results are presented of experiments on depositing charged particles, which imitate the levitating dust on the Moon, on stainless steel. Ensembles of particles are created above the surface of laboratory regolith whose composition and particle size distribution imitate the dust that covers the Moon's surface. Under the action of the gyrotron radiation on regolith, non-linear physical-chemical processes develop (breakdown, chain plasmachemical reactions, and particle scattering by the Coulomb mechanism), which lead to the appearance of a levitating cloud of particles. The simulation experiment is based on the similarity between the processes that develop in the laboratory experiments with regolith and the processes that occur on the Moon during its bombardment by micrometeorites. The effect of the levitating cloud on stainless steel plates is studied and it is shown that regolith particles in the shape of spheroids of different sizes are deposited on the surface of the plates. The dimensions of the deposited particles and the density of their placement depend on the quality of treatment of the plate surface. It is shown that the laboratory-produced dusty plasma can be used in simulation experiments to study the modification of surfaces of different materials for space technology.

4.
Curr Drug Discov Technol ; 15(4): 335-350, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29468977

RESUMO

BACKGROUND: Factor Xa (FXa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation. OBJECTIVE: Our approach for the development of directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in this work. METHOD: Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening methods, where R1, R2 and R3 are some chemical groups and (CONH) are amide bonds connecting R1, R2 and R3. The direction of amide bond (CONH) could be arbitrary for R1, R2 and R2, R3. RESULTS: Chemical modifications were made in the frame of the results, taking into account the structure of FXa, chemical synthesis capabilities, as well as patentability of the target compounds. Subnanomolar potency of several developed compounds was achieved. Several analyzers and various testing-suites have been used to measure the concentration that doubled the prothrombin time (PTx2). Moreover, in human plasma the PTx2 concentration of the compound 217 (DD217) turned out to be 80±20 nM. The compound efficacy has proved by in vivo assays including oral administrations in rats, rabbits and monkeys. CONCLUSION: The pharmacodynamic profile of DD217 for oral administration in cynomolgus monkeys proves the efficacy of the compound, which makes it promising for the future preclinical trials.


Assuntos
Amidas/síntese química , Desenvolvimento de Medicamentos/métodos , Inibidores do Fator Xa/síntese química , Administração Oral , Amidas/farmacologia , Animais , Bioensaio/métodos , Coagulação Sanguínea/efeitos dos fármacos , Química Farmacêutica/métodos , Avaliação Pré-Clínica de Medicamentos , Fator Xa/metabolismo , Inibidores do Fator Xa/farmacologia , Humanos , Macaca fascicularis , Modelos Animais , Plasma , Tempo de Protrombina , Coelhos , Ratos
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