1,4 - dihidropiridīnu atvasinājuma AV-6-93, tā struktūras analoga un struktūras elementu darbības izpēte MPP+ toksicitātes modelī SH-SY5Y šūnās
Date
2013
Authors
Surgovte, Līva
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Publisher
Latvijas Universitāte
Abstract
Mitohondriju protekcijai ir nozīmīga loma neirodeģeneratīvo slimību attīstības mazināšanā. Šī darba mērķis bija noskaidrot Latvijas Organiskās sintēzes institūtā sintezētā 1,4-dihidropiridīnu (DHP) atvasinājuma AV-6-93, tā analoga un struktūras elementu, kā arī 1-aminoadamantāna spēju mazināt mitohondriju toksīna 1-metil-4-fenilpiridīna (MPP+) izraisītu nāvi SH-SY5Y šūnās.
Rezultāti parādīja, ka AV-6-93 (0,1-10,0 ĀM) un tā struktūras analogs V-2-66 (10,0 ĀM) pievienoti per se palielināja šūnu dzīvotspēju. Šie savienojumi (10,0 ĀM) pastiprināja, savukārt, AV-6-93 (0,1 ĀM) samazināja MPP+ izraisītu šūnu nāvi. AV-6-93 struktūras elementi neietekmēja ne šūnu dzīvotspēju pievienoti per se, ne MPP+ izraisīto toksicitāti. 1-aminoadamantāns (10,0 ĀM) samazināja MPP+ izraisītu šūnu nāvi. AV-6-93 izraisītos efektus nodrošina tā struktūra kopumā.
Mitochondrial protection play significant role in neuroprotection. The aim was to study the ability of 1,4-dihydropyridine (DHP) derivative AV-6-93, it’s analogue and elements of the structure, and 1-aminoadamantane to reduce 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell death. Compounds were synthesized at the Latvian Institute of Organic Synthesis. The results showed that the AV-6-93 (0,1-10,0 ĀM) and it’s analogue V-2-66 (10,0 ĀM) added per se augmented cell viability. Both of these compounds (10,0 ĀM) increased, while AV-6-93 (10,0 ĀM) decreased MPP+-induced cell death. Structure elements of AV-6-93 added per se did not affect neither cell viability, nor MPP+-induced toxicity. 1-aminoadamantane (10,0 ĀM) decreased MPP+-induced cell death. Obtained data indicate, that structure of AV-6-93 as a whole provides its activities.
Mitochondrial protection play significant role in neuroprotection. The aim was to study the ability of 1,4-dihydropyridine (DHP) derivative AV-6-93, it’s analogue and elements of the structure, and 1-aminoadamantane to reduce 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell death. Compounds were synthesized at the Latvian Institute of Organic Synthesis. The results showed that the AV-6-93 (0,1-10,0 ĀM) and it’s analogue V-2-66 (10,0 ĀM) added per se augmented cell viability. Both of these compounds (10,0 ĀM) increased, while AV-6-93 (10,0 ĀM) decreased MPP+-induced cell death. Structure elements of AV-6-93 added per se did not affect neither cell viability, nor MPP+-induced toxicity. 1-aminoadamantane (10,0 ĀM) decreased MPP+-induced cell death. Obtained data indicate, that structure of AV-6-93 as a whole provides its activities.
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