Radiation-Thermal Synthesis of Copolymers of Chitosan with Acrylamide as a Means of Betulin Delivering

Радиационно-термическим методом с использованием ускоренных электронов получены привитые сополимеры хитозана с акриламидом. Образование привитых сополимеров подтверждено методами ИК‑спектроскопии и гель-проникающей хроматографии. Показано, что эффективность и степень прививки зависят от дозы ионизирующего облучения и с ростом дозы проходят через максимум. Найдены условия получения сополимеров с высоким выходом продукта. Полученные сополимеры использованы для получения композитов бетулина с помощью механохимической обработки. Показано, что скорость выделения бетулина в водный раствор при растворении композита зависит от pH раствора, что позволяет рассматривать механокомпозиты на основе сополимеров хитозана с акриламидом как перспективные средства для контролируемой доставки лекарственных веществGraft copolymers of chitosan with acrylamide were obtained by the radiation-thermal method using accelerated electrons. The formation of graft copolymers was confirmed by IR spectroscopy and gel permeation chromatography. It is shown that the efficiency and degree of grafting depend on the dose of ionizing radiation, and pass through a maximum with increasing dose. The conditions for obtaining copolymers with a high yield of the product were found. The resulting copolymers were used to obtain betulin composites using mechanochemical processing. It has been shown that the rate of release of betulin into an aqueous solution during the dissolution of the composite depends on the pH of the solution, which makes it possible to consider mechanocomposites based on copolymers of chitosan with acrylamide as promising means for controlled drug deliver

Virescenosides from the Holothurian-Associated Fungus Acremonium striatisporum Kmm 4401

Ten new diterpene glycosides virescenosides Z9-Z18 (1–10) together with three known analogues (11–13) and aglycon of virescenoside A (14) were isolated from the marine-derived fungus Acremonium striatisporum KMM 4401. These compounds were obtained by cultivating fungus on wort agar medium with the addition of potassium bromide. Structures of the isolated metabolites were established based on spectroscopic methods. The effects of some isolated glycosides and aglycons 15–18 on urease activity and regulation of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) production in macrophages stimulated with lipopolysaccharide (LPC) were evaluated

New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide

Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (1) from the marine-derived fungus Penicillium dimorphosporum KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound 1 is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound 1 resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes