Ammonium-Charged Sterically Hindered Phenols with Antioxidant and Selective Anti-Gram-Positive Bacterial Activity

© 2020 Wiley-VHCA AG, Zurich, Switzerland The increase in the resistance of pathogens, in particular Staphylococcus aureus, to the action of antibiotics necessitates the search for new readily available and non-toxic drugs. In solving this problem, phenolic acylhydrazones have high potential. In this communication, the synthesis of quaternary ammonium compounds containing a differently substituted phenolic moiety has been performed. An initial study of antimicrobial activity showed that these compounds are highly selective against S. aureus and B. cereus. The highest activity (MIC 2.0 μm) was shown by hydrazones containing a catechol fragment. These compounds are more than 3-fold more active against S. aureus and 3–10-fold more active against B. cereus than norfloxacin. Low hemolytic and high antioxidant activities of all new compounds were also established

Design and synthesis of amphiphilic 2-hydroxybenzylphosphonium salts with antimicrobial and antitumor dual action

© 2020 Elsevier Ltd Here we report the synthesis and biological evaluation of a series of new 2-hydroxybenzylphosphonium salts (QPS) with antimicrobial and antitumor dual action. The most active compounds exhibit antimicrobial activity at a micromolar level against Gram-positive bacteria Sa (ATCC 209p and clinical isolates), Bc (1–2 μM) and fungi Tm and Ca, and induced no notable hemolysis at MIC. The change in nature of substituents of the same length led to a drastic change of biological activity. Self-assembly behavior of the octadecyl and oleyl derivatives was studied. QPS demonstrated self-assembly within the micromolar range with the formation of nanosized aggregates capable of the solubilizing hydrophobic probe. The synthesized phosphonium salts were tested for cytotoxicity. The most potent salt was active against on M−Hela cell line with IC50 on the level of doxorubicin and good selectivity. According to the cytofluorimetry analysis, the salts induced mitochondria-dependent apoptosis

Identification of exponential trend models with fractional white noise

В статье предложены алгоритмы для идентификации параметров экспоненциальных трендовых моделей при наличии дробным белым шума. В статье рассмотрено три вида моделей, являющихся решения однородного линейного дифференциального уравнения второго порядка. Идентификация решения дифференциального уравнения позволяет повысить точность за счет учета априорной информации о характере корней дифференциального уравнения и начальных условиях. Однако идентификация решения сопряжена с трудностями, связанными с нелинейностью по параметрам, получаемых решений. Предложены двухшаговые алгоритмы, позволяющие определять оценки параметров, рассматриваемых трендовых моделей. Тестовые примеры показали высокую точность оценок, получаемых с помощью разработанных алгоритмов. The paper suggests algorithms for identifying parameters of exponential trend models in the presence of fractional white noise. The paper considers three types of models that are solutions of a homogeneous linear differential equation of the second order. Identification of the solution of a differential equation makes it possible to increase accuracy by taking into account a priori information about the nature of the roots of the differential equation and initial conditions. However, identification of the solution is fraught with difficulties due to nonlinearity in the parameters of the obtained solutions. Two-step algorithms are proposed, allowing to determine the estimates of the parameters of the considered trend models. Test examples showed high accuracy of the estimates obtained using the developed algorithms

Trialkyl(vinyl)phosphonium Chlorophenol Derivatives as Potent Mitochondrial Uncouplers and Antibacterial Agents

Trialkyl phosphonium derivatives of vinyl-substituted p-chlorophenol were synthesized here by a recently developed method of preparing quaternary phosphonium salts from phosphine oxides using Grignard reagents. All the derivatives with a number (n) of carbon atoms in phosphonium alkyl substituents varying from 4 to 7 showed pronounced uncoupling activity in isolated rat liver mitochondria at micromolar concentrations, with a tripentyl derivative being the most effective both in accelerating respiration and causing membrane potential collapse, as well as in provoking mitochondrial swelling in a potassium-acetate medium. Remarkably, the trialkyl phosphonium derivatives with n from 4 to 7 also proved to be rather potent antibacterial agents. Methylation of the chlorophenol hydroxyl group suppressed the effects of P555 and P444 on the respiration and membrane potential of mitochondria but not those of P666, thereby suggesting a mechanistic difference in the mitochondrial uncoupling by these derivatives, which was predominantly protonophoric (carrier-like) in the case of P555 and P444 but detergent-like with P666. The latter was confirmed by the carboxyfluorescein leakage assay on model liposomal membranes