Структура и биологическое действие аналогов и производных биогенных полиаминов

Objectives. Biogenic polyamines are widely present in nature. They are characteristic of both protozoan cells and multicellular organisms. These compounds have a wide range of biological functions and are necessary for normal growth and development of cells. Violation of polyamine homeostasis can cause significant abnormalities in cell functioning, provoking various pathological processes, including oncological and neuropsychiatric diseases. The impact on the “polyamine pathway” is an attractive basis for the creation of many pharmacological agents with a diverse spectrum of action. The purpose of this review is to summarize the results of the studies devoted to understanding the biological activity of compounds of the polyamine series, comparing their biological action with action on certain molecular targets. Due to the structural diversity of this group of substances, it is impossible to fully reflect the currently available data in one review. Therefore, in this work, the main attention is paid to the derivatives, acyclic saturated polyamines.Results. The following aspects are considered: biological functionality, biosynthesis and catabolism, cell transport, and localization of biogenic polyamines in the living systems. Structural analogs and derivatives of biogenic polyamines with antitumor, neuroprotective, antiarrhythmic, antiparasitic, antibacterial, and other biological activities are represented; the relationship between biological activity and the target of exposure is reflected. It was found that the nature of the substituent, the number of cationic centers, and the length of the polyamine chain have a great influence on the nature of the effect.Conclusions. At present, the use of polyamine structures is restrained by cytotoxicity and nonspecific toxic effects on the central nervous system. Further research in the field of biochemistry, cell transport, and a deeper understanding of receptor interaction mechanisms will help making polyamines as the basis for potential drug formulation.Цели. Биогенные полиамины широко представлены в живой природе. Они характерны как для клеток простейших, так и для многоклеточных организмов. Данные соединения обладают широким спектром биологической активности и необходимы для нормального роста и развития клеток. Нарушение гомеостаза полиаминов может вызывать существенные отклонения в функционировании клетки, провоцируя протекание патологических процессов различного рода, включая онкологические и психоневрологические заболевания. Воздействие на «полиаминовый путь» является привлекательным базисом для создания ряда фармакологически активных веществ с различным спектром действия. Целью данного обзора является обобщение результатов исследований, посвященных изучению биологической активности соединений полиаминового ряда; сопоставление биологического действия с воздействием на определенные молекулярные мишени. В виду структурного многообразия данной группы веществ невозможно в полной мере отразить имеющиеся на сегодняшний момент данные в одном обзоре. Поэтому в настоящей работе основное внимание уделено производным насыщенных полиаминов ациклического строения.Результаты. В общем виде рассмотрены следующие аспекты: биологическая активность, биосинтез и катаболизм, клеточный транспорт и локализация биогенных полиаминов в живых системах. Представлены структурные аналоги и производные биогенных полиаминов, обладающие противоопухолевой, нейропротекторной, антиаритмической, противопаразитарной, антибактериальной и некоторыми другими видам биологической активности; отражена взаимосвязь между биологической активностью и мишенями воздействия. Установлено, что на характер воздействия большое влияние оказывает природа заместителя, количество катионных центров, а также длина полиаминовой цепи.Выводы. В настоящее время применение структур полиаминового ряда сдерживается наличием цитотоксичности, а также неспецифического токсического воздействия на ЦНС. Дальнейшие исследования в области биохимии, клеточного транспорта, а также более глубокое понимание механизмов рецепторного взаимодействия позволят использовать полиамины в качестве основы для создания потенциальных лекарственных препаратов

New Apatite Fission-Track Data from the Murmansk Craton, NE Fennoscandia: An Echo of Hidden Thermotectonic Events

For a long time, the thermal history of northeastern (NE) Fennoscandia in the Phanerozoic and Precambrian remained unknown, since no thermochronological studies were carried out within the Kola Peninsula area. Two years ago, we developed the first model of tectono-thermal evolution of the Kola Peninsula territory for the last 1.9 Gyr using a set of newly obtained apatite fission-track (AFT) and Ar/Ar thermochronological data. However, the low-temperature history of the most ancient tectonic unit of the northeastern part of the Kola Peninsula—the Archean Murmansk craton—remained poorly constrained due to the lack of AFT data. In this paper, we present the first results of AFT studies of 14 samples representing intrusive and metamorphic Precambrian rocks, located within the Murmansk craton of NE Fennoscandia. AFT ages and track length distributions indicate a similar tectono-thermal evolution of Precambrian tectonic units in NE Fennoscandia over the last 300 Myr. The AFT ages are distributed between ca. 177 and ca. 384 Ma; their median value, ~293 Ma, confirms the presence of a previously identified hidden thermal event that took place at about 300 Ma. However, a detailed analysis of the AFT age distribution shows the presence of three statistically distinguishable age components: 180–190 Ma (C1), 290–320 Ma (C2) and 422 Ma (C3). We assume that the relatively young AFT ages of C1 may originate from apatite crystals with low thermal resistivity. Remarkably, this value coincides with the initial stage of the Barents Sea magmatic province activity during large-scale plume-lithospheric interaction, as well as with the assumed age of an enigmatic remagnetization event throughout the Kola Peninsula. C2 ages can be observed in both the gabbroic and non-gabbroic samples, whereas C3 ages can only be found in gabbro. It is supposed that C2 ages, similarly to the Central Kola terrane, correspond to a cooling event related to the denudation of a thick sedimentary cover, representing a continuation of the Caledonian foreland basin towards NE Fennoscandia. C3 ages may be associated with a thermal event corresponding to the Caledonian collisional orogeny

New Apatite Fission-Track Data from the Murmansk Craton, NE Fennoscandia: An Echo of Hidden Thermotectonic Events

For a long time, the thermal history of northeastern (NE) Fennoscandia in the Phanerozoic and Precambrian remained unknown, since no thermochronological studies were carried out within the Kola Peninsula area. Two years ago, we developed the first model of tectono-thermal evolution of the Kola Peninsula territory for the last 1.9 Gyr using a set of newly obtained apatite fission-track (AFT) and Ar/Ar thermochronological data. However, the low-temperature history of the most ancient tectonic unit of the northeastern part of the Kola Peninsula—the Archean Murmansk craton—remained poorly constrained due to the lack of AFT data. In this paper, we present the first results of AFT studies of 14 samples representing intrusive and metamorphic Precambrian rocks, located within the Murmansk craton of NE Fennoscandia. AFT ages and track length distributions indicate a similar tectono-thermal evolution of Precambrian tectonic units in NE Fennoscandia over the last 300 Myr. The AFT ages are distributed between ca. 177 and ca. 384 Ma; their median value, ~293 Ma, confirms the presence of a previously identified hidden thermal event that took place at about 300 Ma. However, a detailed analysis of the AFT age distribution shows the presence of three statistically distinguishable age components: 180–190 Ma (C1), 290–320 Ma (C2) and 422 Ma (C3). We assume that the relatively young AFT ages of C1 may originate from apatite crystals with low thermal resistivity. Remarkably, this value coincides with the initial stage of the Barents Sea magmatic province activity during large-scale plume-lithospheric interaction, as well as with the assumed age of an enigmatic remagnetization event throughout the Kola Peninsula. C2 ages can be observed in both the gabbroic and non-gabbroic samples, whereas C3 ages can only be found in gabbro. It is supposed that C2 ages, similarly to the Central Kola terrane, correspond to a cooling event related to the denudation of a thick sedimentary cover, representing a continuation of the Caledonian foreland basin towards NE Fennoscandia. C3 ages may be associated with a thermal event corresponding to the Caledonian collisional orogeny

1.86 Ga key paleomagnetic pole from the Murmansk craton intrusions – Eastern Murman Sill Province, NE Fennoscandia: Multidisciplinary approach and paleotectonic applications

© 2019 Elsevier B.V. We present the first 1.86 Ga paleomagnetic key pole of Fennoscandia obtained for the dolerite sills of the Murmansk craton – Eastern Murman Sill Province, that outcrop in the northern part of the Kola Peninsula along the Barents Sea coast for a distance of 200 km (Slat = 68.5°; Slong = 37.9°; N = 16 sites; Plat = 54.7°; Plong = 234.7°; dp/dm = 4.3°/6.3° Qv = 5). The age of the sills and their characteristic remanent magnetization (ChRM) was determined by four independent geochronometers: U-Pb – 1860 ± 4 and 1863 ± 7 Ma (ID-TIMS, baddeleyite), Sm-Nd – 1889 ± 57 Ma, Rb-Sr – 1850 Ma, Ar/Ar – 1865 ± 8 and 1857 ± 20 Ma (biotite). The primary nature of the ChRM is confirmed by the results of petrographic, geochemical, paleo- and rock magnetic studies, as well as by thermochronological data. The similarity of the petrographic and geochemical characteristics of sills from different localities indicates that these dolerite sills were formed during a single magmatic event and their cooling down to 580 °C occurred at depths of about 10 ± 2 km and lasted ∼2800 years or even faster. Paleogeographic reconstruction of Fennoscandia on the basis of the obtained paleomagnetic pole is in general agreement with the previously suggested configuration of core of the Nuna/Columbia supercontinent (Evans and Mitchell, 2011; Meert and Santosh, 2017). A new reliable Thellier-Coe paleointensity determination for this time reveals a rather low mean VDM = 1.8 (±0.1) × 10 22 Am 2 that supports the Proterozoic dipole low hypothesis (Biggin et al., 2009)

1.86 Ga key paleomagnetic pole from the Murmansk craton intrusions – Eastern Murman Sill Province, NE Fennoscandia: Multidisciplinary approach and paleotectonic applications

© 2019 Elsevier B.V. We present the first 1.86 Ga paleomagnetic key pole of Fennoscandia obtained for the dolerite sills of the Murmansk craton – Eastern Murman Sill Province, that outcrop in the northern part of the Kola Peninsula along the Barents Sea coast for a distance of 200 km (Slat = 68.5°; Slong = 37.9°; N = 16 sites; Plat = 54.7°; Plong = 234.7°; dp/dm = 4.3°/6.3° Qv = 5). The age of the sills and their characteristic remanent magnetization (ChRM) was determined by four independent geochronometers: U-Pb – 1860 ± 4 and 1863 ± 7 Ma (ID-TIMS, baddeleyite), Sm-Nd – 1889 ± 57 Ma, Rb-Sr – 1850 Ma, Ar/Ar – 1865 ± 8 and 1857 ± 20 Ma (biotite). The primary nature of the ChRM is confirmed by the results of petrographic, geochemical, paleo- and rock magnetic studies, as well as by thermochronological data. The similarity of the petrographic and geochemical characteristics of sills from different localities indicates that these dolerite sills were formed during a single magmatic event and their cooling down to 580 °C occurred at depths of about 10 ± 2 km and lasted ∼2800 years or even faster. Paleogeographic reconstruction of Fennoscandia on the basis of the obtained paleomagnetic pole is in general agreement with the previously suggested configuration of core of the Nuna/Columbia supercontinent (Evans and Mitchell, 2011; Meert and Santosh, 2017). A new reliable Thellier-Coe paleointensity determination for this time reveals a rather low mean VDM = 1.8 (±0.1) × 10 22 Am 2 that supports the Proterozoic dipole low hypothesis (Biggin et al., 2009)