Determination and pharmacokinetic study of isothiouronium-modified pyrimidine-substituted curcumin analog (1G), a novel antitumor agent, in rat plasma by liquid chromatography–tandem mass spectrometry

Sun, Jialin; Wang, Jinpeng; Ma, Lin; Jiang, Tao; Xiao, Li; Guo, Qie; Li, Xiangpeng; Sui, Zhongguo

doi:10.1080/21691401.2019.1602537

Cited by 1 publication

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“…Благодаря высокой вариативности структурных модификаций тиурониевые соли проявляют широкий спектр биологической активности [4]. Среди них можно выделить ингибиторы NO-синтазы [5,6], соединения, обладающие антимикробным [6,7], противоопухолевым действием [8][9][10][11], ингибиторы Н2-и Н3-гистаминных рецепторов [12,13]. Производные тиомочевин способны образовывать стабильные комплексы с ионами различных металлов.…”

Section: Introductionunclassified

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Lozinskaya

Морозов

Bazanov

et al. 2023

Bezopasnost' i risk farmakoterapii

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Most of the medicinal products that are currently approved and used in clinical practice for neurodegenerative diseases, in particular Alzheimer’s disease, have a compensatory mechanism of action that enhances neurotransmitter signalling. It is an urgent need to develop new medicinal products combining cognitive-enhancing, neuroprotective, and disease-specific effects resulting from a multi-target mechanism of action including, in particular, prevention of glutamate-induced neuronal calcium uptake and stabilisation of microtubules.The aim of this study was to search for potentially neuroprotective and tauopathy-alleviating medicines amongst new thiouronium salt derivatives based on vicinal diamines.Materials and methods. The study investigated the ability of thiouronium salts to block glutamate-induced 45Ca2+ uptake by synaptosomes prepared from the brain of Wistar rats. The authors evaluated effects of these new compounds on polymerisation of a preparation of C57bl mouse brain tubulin and microtubule-associated proteins. The evaluation was carried out in the presence of guanosine triphosphate (GTP) and based on specific absorbance changes at 355 nm due to formation of microtubules. The authors analysed the structure of these microtubules, using negative staining followed by transmission electron microscopy. The IC50 determination and the statistical analysis were performed using standard software (Excel and PRISM 6.02).Results. The authors developed a screening algorithm for a number of new thiouronium salt derivatives based on vicinal diamines and studied biological activity of these derivatives by the effects on glutamate-induced calcium uptake by synaptosomes and on microtubule assembly processes. The authors identified compounds suppressing glutamate-induced calcium uptake by synaptosomes, i.e. compounds with neuroprotective potential. In addition, a number of new compounds were able to stimulate GTP-dependent microtubule assembly processes. The authors observed formation of microtubules with a normal structure in the presence of isopropyl-N’-[2-(benzoylamino)-1,2-diphenylethyl]-N-ethylimidothiocarbamate hydrobromide and considered the compound a promising scaffold for further optimisation.Conclusions. Chemical modification of thiouronium salts is a promising direction for developing effective neuroprotectors and microtubule stabilisers.

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Section: Introductionunclassified

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Lozinskaya

Морозов

Bazanov

et al. 2023

Bezopasnost' i risk farmakoterapii

View full text Add to dashboard Cite

show abstract

Determination and pharmacokinetic study of isothiouronium-modified pyrimidine-substituted curcumin analog (1G), a novel antitumor agent, in rat plasma by liquid chromatography–tandem mass spectrometry

Abstract: Sui (2019) Determination and pharmacokinetic study of isothiouronium-modified pyrimidine-substituted curcumin analog (1G), a novel antitumor agent, in rat plasma by liquid chromatography-tandem mass spectrometry,

Cited by 1 publication

References 25 publications

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

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