Jaunu Stirilpiridīnija grupu saturošu savienojumu – sintēze, fizikāli ķīmisko, pašsavienojošo un bioloģisko īpašību novērtēšana.
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Date
2023
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Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Mērķi.
Stirilpiridīnija sāļi tiek plaši pētīti gan kā attēlveidošanas līdzekļi bioķīmiskiem, biofizikāliem un molekulārās bioloģijas lietojumiem to fluorescējošu īpašību dēļ [Dubur et al 1984, Xu et al, 2015], gan kā perspektīvi savienojumi ar bioloģiskām īpašībām, piemēram, pretmikrobu iedarbību. [Vaitkiene et al, 2020]. Jaunu savienojumu izstrāde ar vēlamām fotofizikālām īpašībām ir izaicinājums pētniekiem, kas strādā šajā jomā.
Darba mērķis bija jaunu stirilpiridīnija atvasinājumu sintēze un to fizikālo, pašsavienojošo un bioloģisko īpašību novērtēšana.
Materiāli un metodes.
Stirilpiridīnija atvasinājumi tika sintezēti no atbilstošiem aldehīdiem un 4-pikolīnija sāļiem saskaņā ar [Vaitkiene et al, 2020] vai no atbilstošiem aldehīdiem un 4-pikolīna [Lorance et al, 2002] ar sekojošu kvaternizāciju. Pašsavienojošās īpašības tika novērtētas izmantojot dinamiskās gaismas izkliedes metodi; paraugi tika sagatavoti ar injekcijas metodi kā ūdens šķīdumi. [Pajuste et al, 2013]
Savienojumu citotoksicitāte in vitro tika novērtēta ar MTT testu uz audzēja šūnu līnijām – HT-1080 un MH-22A un normāliem peles fibroblastiem 3T3. [Strokes et al, 2008]. Lai analizētu šūnu fluorescenci, tika izmantota fluorescējošā mikroskopija.
Rezultāti.
Oriģinālo stirilpiridīnija krāsvielu komponenti ar strukturālām variācijām tika iegūti, izmantojot divas iepriekš aprakstītās metodes.
Nanodaļiņas ar vidējo izmēru ap 120 nm veidoja svaigi sagatavoti paraugi. Pārbaudītie savienojumi uzrāda intensīvu fluorescenci, īpaši lipofilā vidē. Dažām stirilpiridīnija krāsvielām bija nozīmīga selektīva antiproliferatīva aktivitāte vēža šūnu līnijās (HT-1080; MH-22A), kā arī zema citotoksicitāte nevēža NIH3T3 šūnās. Ar dažiem savienojumiem iepriekš inkubētu šūnu fluorescējošā mikroskopija atklāja intensīvu sarkano fluorescenci, kas tika novērota vismaz 5 dienu laikā pēc kultivēšanas.
Secinājumi.
Sintezēto savienojumu struktūras atšķirības spēcīgi ietekmē pārbaudīto stirilpiridīnija atvasinājumu īpašības.
Objectives. Styrylpyridinium salts are widely studied both as imaging agents for biochemical, biophysical, molecular biology applications due to fluorescent properties [Dubur et al 1984, Xu et al, 2015] and as prospective compounds with biological properties, for example antimicrobial activity. [Vaitkiene et al, 2020]. The development of new compounds with desirable photophysical properties is a challenge for the researchers working in this field. The aim of the study was synthesis and evaluation of physical, self-assembling and biological properties of new styrylpyridinium derivatives. Materials and Methods. Styrylpyridinium derivatives were synthesized from the appropriate aldehydes and 4-picolinium salts according to [Vaitkiene et al, 2020] or from appropriate aldehydes and 4-picoline [Lorance et al, 2002] with following quaternization. Dynamic light scattering method was used for self-assembling estimation; samples were prepared by tin film hydration method as aqueous solutions. [Pajuste et al, 2013] Cytotoxicity of compounds in vitro was assessed by the MTT test on tumor cell lines – HT-1080 and MH-22A and normal mouse fibroblasts 3T3. [Strokes et al, 2008]. Fluorescent microscopy was used to analyze cell fluorescence. Results. Set of original styrylpyridinium dyes with structure variations was obtained using two above described approaches. Nanoparticles with the average size around 120 nm were formed by freshly prepared samples. The tested compounds show an intensive fluorescence, especially in lipophylic medium. The some of styrylpyridinium dyes possessed significant selective antiproliferative activity in cancer cell lines (HT-1080; MH-22A) together with low cytotoxicity in noncancerous NIH3T3 cells. Fluorescent microscopy of cells preincubated with some compounds revealed an intense red fluorescence monitored within at least 5 days of cultivation. Conclusions. Structure variation in the synthesized compounds strongly affects the properties of the tested styrylpyridinium derivatives.
Objectives. Styrylpyridinium salts are widely studied both as imaging agents for biochemical, biophysical, molecular biology applications due to fluorescent properties [Dubur et al 1984, Xu et al, 2015] and as prospective compounds with biological properties, for example antimicrobial activity. [Vaitkiene et al, 2020]. The development of new compounds with desirable photophysical properties is a challenge for the researchers working in this field. The aim of the study was synthesis and evaluation of physical, self-assembling and biological properties of new styrylpyridinium derivatives. Materials and Methods. Styrylpyridinium derivatives were synthesized from the appropriate aldehydes and 4-picolinium salts according to [Vaitkiene et al, 2020] or from appropriate aldehydes and 4-picoline [Lorance et al, 2002] with following quaternization. Dynamic light scattering method was used for self-assembling estimation; samples were prepared by tin film hydration method as aqueous solutions. [Pajuste et al, 2013] Cytotoxicity of compounds in vitro was assessed by the MTT test on tumor cell lines – HT-1080 and MH-22A and normal mouse fibroblasts 3T3. [Strokes et al, 2008]. Fluorescent microscopy was used to analyze cell fluorescence. Results. Set of original styrylpyridinium dyes with structure variations was obtained using two above described approaches. Nanoparticles with the average size around 120 nm were formed by freshly prepared samples. The tested compounds show an intensive fluorescence, especially in lipophylic medium. The some of styrylpyridinium dyes possessed significant selective antiproliferative activity in cancer cell lines (HT-1080; MH-22A) together with low cytotoxicity in noncancerous NIH3T3 cells. Fluorescent microscopy of cells preincubated with some compounds revealed an intense red fluorescence monitored within at least 5 days of cultivation. Conclusions. Structure variation in the synthesized compounds strongly affects the properties of the tested styrylpyridinium derivatives.
Description
Farmācija
Pharmacy
Veselības aprūpe
Health Care
Pharmacy
Veselības aprūpe
Health Care
Keywords
Stirilpiridīnija atvasinājumi; Pašveidojošās īpašības; Nanodaļiņas; Dinamiskā gaismas izkliede; Fluorescējošās īpašības, Styrylpyridinium derivatives; Self-assembling properties; Nanoparticles; Dynamic light scattering; Fluorescent properties