New original metabolitotropic endothelioprotector "Angiolin": quantum-chemical parameters and peculiarities of pharmacological action

Чекман, И. С.; Kazakova, O. A.; Mazur, I. A.; Nagornaya, E. A.; Бєленічев, Ігор Федорович; Gorchakova, N. A.; Buhtiyarova, N.V.; Syrova, A.O.; Dovhan, R.S.; Zahorodnyi, M.I.

doi:10.15407/dopovidi2017.08.086

Cited by 3 publications

(4 citation statements)

References 8 publications

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“…The course administration of Angiolin to animals with chronic cerebral ischemia leads to a decrease in mitochondria with signs of ultrastructural disorders in the CA1 zone of the hippocampus, which may indicate a mitoprotective link in the neuroprotective mechanism of action of the drug. The mechanism of this action is due to the ability of the L-lysine metabolite -pipecolic acid to limit transmitter autokoidosis and due to the properties of Angiolin to activate compensatory mechanisms, to inactivate cytotoxic forms of NO, to inhibit the NO-dependent mechanism of neuroapoptosis and to increase the bioavailability of this transmitter (Chekman et al, 2017). Also, due to its antioxidant properties, Angiolin is able to influence ROSand SH-SS-dependent mechanisms of Red/Oxi regulation and transcription, which can lead to an increase in HSP70 expression.…”

Section: Sodium Selenitementioning

confidence: 99%

“…The mechanism of this action is due to the ability of the L-lysine metabolite – pipecolic acid to limit transmitter autokoidosis and due to the properties of Angiolin to activate compensatory mechanisms, to inactivate cytotoxic forms of NO, to inhibit the NO-dependent mechanism of neuroapoptosis and to increase the bioavailability of this transmitter ( Chekman et al, 2017 ). Also, due to its antioxidant properties, Angiolin is able to influence ROS- and SH-SS-dependent mechanisms of Red/Oxi regulation and transcription, which can lead to an increase in HSP70 expression.…”

Section: Possible Pathways For Activation Of Hsp70-dependent Mechanis...mentioning

confidence: 99%

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Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

Беленичев

Aliyeva

Popazova

et al. 2023

Front. Cell. Neurosci.

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This analytical review summarizes literature data and our own research on HSP70-dependent mechanisms of neuroprotection and discusses potential pharmacological agents that can influence HSP70 expression to improve neurological outcomes and effective therapy. The authors formed a systemic concepts of the role of HSP70-dependent mechanisms of endogenous neuroprotection aimed at stopping the formation of mitochondrial dysfunction, activation of apoptosis, desensitization of estrogen receptors, reduction of oxidative and nitrosative stress, prevention of morpho-functional changes in brain cells during cerebral ischemia, and experimentally substantiated new target links for neuroprotection. Heat shock proteins (HSPs) are an evolutionarily integral part of the functioning of all cells acting as intracellular chaperones that support cell proteostasis under normal and various stress conditions (hyperthermia, hypoxia, oxidative stress, radiation, etc.). The greatest curiosity in conditions of ischemic brain damage is the HSP70 protein, as an important component of the endogenous neuroprotection system, which, first of all, performs the function of intracellular chaperones and ensures the processes of folding, holding and transport of synthesized proteins, as well as their degradation, both under normoxic conditions and stress-induced denaturation. A direct neuroprotective effect of HSP70 has been established, which is realized through the regulation the processes of apoptosis and cell necrosis due to a long-term effect on the synthesis of antioxidant enzymes, chaperone activity, and stabilization of active enzymes. An increase in the level of HSP70 leads to the normalization of the glutathione link of the thiol-disulfide system and an increase in the resistance of cells to ischemia. HSP 70 is able to activate and regulate compensatory ATP synthesis pathways during ischemia. It was found that in response to the cerebral ischemia formation, HIF-1a is expressed, which initiates the launch of compensatory mechanisms for energy production. Subsequently, the regulation of these processes switches to HSP70, which “prolongs” the action of HIF-1a, and also independently maintains the expression of mitochondrial NAD-dependent malate dehydrogenase activity, thereby maintaining the activity of the malate-aspartate shuttle mechanism for a long time. During ischemia of organs and tissues, HSP70 performs a protective function, which is realized through increased synthesis of antioxidant enzymes, stabilization of oxidatively damaged macromolecules, and direct anti-apoptotic and mitoprotective action. Such a role of these proteins in cellular reactions during ischemia raises the question of the development of new neuroprotective agents which are able to provide modulation/protection of the genes encoding the synthesis of HSP 70 and HIF-1a proteins. Numerous studies of recent years have noted the important role of HSP70 in the implementation of the mechanisms of metabolic adaptation, neuroplasticity and neuroprotection of brain cells, so the positive modulation of the HSP70 system is a perspective concept of neuroprotection, which can improve the efficiency of the treatment of ischemic-hypoxic brain damage and be the basis for substantiating of the feasibility of using of HSP70 modulators as promising neuroprotectors.

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Section: Sodium Selenitementioning

confidence: 99%

Section: Possible Pathways For Activation Of Hsp70-dependent Mechanis...mentioning

confidence: 99%

Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

Беленичев

Aliyeva

Popazova

et al. 2023

Front. Cell. Neurosci.

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“…Wang H. et al (2009) found that eNOS expression was reduced after OGD reperfusion injury. Yagita et al, 2013 showed that eNOS dysfunction leads to endothelial dysfunction and inhibits tissue repair after ischemic injury [37].…”

Section: Fig 1 Relative Normalized Expression Of Mrna Of (A) Nnos mentioning

confidence: 99%

Long-Term Results of Pharmacological Correction of Inos, Enos, Nnos Mrna Expression Disorders in Rat Hippocampus After Chronic Prenatal Hypoxia

Беленичев

Aliyeva

Kamyshnyі

2019

BMFCM

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“…На сьогодні синтезований оригінальний препарат з ендотеліопротективною дією шляхом синтезу активної субстанції (S)-2,6-диаміногексанової кислоти 3-метил-1,2,4-триазоло-5-тіоацетат (робоча назва Ангіолін), яка поєднує у своїй структурі фрагменти молекул тіотриазоліну і L-лізину есцинату і має високі кардіопротективні, протиішемічні, антиоксидантні, нейропротективні та протизапальні властивості [7]. При хронічній серцевій недостатності у щурів Ангіолін більшою мірою, ніж мілдронат, збільшував вміст загальної NOсинтази, L-аргініну, щільність eNOS, зменшував щільність iNOS, рівень метаболітів NO, нітротирозину, відновлював показники тіол-дисульфідної системи (вміст метіоніну, цистеїну, загальних відновлених тіолів, активність глутатіонредуктази, глутатіонпероксидази), підвищував рівень показників енергетичного обміну міокарда щурів (вміст аденілових нуклеотидів, лактату, пірувату, малату, глутамату, аспартату, активність креатинфосфокінази) [8].…”

Section: вступunclassified

Angioline Influence on Metabolic Processes in Experimental Steatohepatitis

Півторак¹,

Yakovleva²

2019

Clin. and experim. pathol.

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New original metabolitotropic endothelioprotector "Angiolin": quantum-chemical parameters and peculiarities of pharmacological action

Cited by 3 publications

References 8 publications

Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: the prospect of using HSP70 modulators

Long-Term Results of Pharmacological Correction of Inos, Enos, Nnos Mrna Expression Disorders in Rat Hippocampus After Chronic Prenatal Hypoxia

Angioline Influence on Metabolic Processes in Experimental Steatohepatitis

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