Cardioprotective Activity of Some 2-Arylimino-1,3-Thiazole Derivatives

Drapak, Іryna; Perekhoda, Lina; Demchenko, Natalya; Suleiman, Marharyta M.; Rakhimova, M. V.; Demchuk, Inna; Taran, Svitlana; Seredynska, N. M.; Gerashchenko, Inna V.

doi:10.3390/scipharm87010007

Cited by 12 publications

(12 citation statements)

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“…15 polysubstituted functionalized aminothiazoles, which antihypertensive activity was determined, were used [6,[8][9]. Calculation of molecular descriptors was carried out using Hyper-Chem 7.5 software [10] (license on HyperChem 7.5 software is available for Danylo Halytsky Lviv National Medical University); BuildQSAR software was used for QSAR-model building [11].…”

Section: Methodsmentioning

confidence: 99%

“…Thiazole derivatives are a promising class for the search for biologically active compounds, since the thiazole nucleus is a strong biophore fragment for the rational design of 'drug-like molecules', and thiazole derivatives exhibit various types of biological activity: antiinflam matory [4], antihypertensive [5], cardioprotective [6], antioxidant [7].…”

Section: Introductionmentioning

confidence: 99%

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Qsar-Analysis of Polysubstituted Functionalized Aminothiazoles With Antihypertensive Activity

Drapak

2020

IJMMR

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Background. QSAR analysis is an important tool for the identification of pharmacophore fragments in biologically active substances and helps optimize the search for new effective drugs. Objective. The aim of the study was to determine the molecular descriptors for QSAR analysis of polysubstituted functionalized aminothiazoles as a theoretical basis for purposeful search de novo of potential antihypertensive drugs among the investigated compounds. Methods. Calculation of molecular descriptors and QSAR-models creation was carried out using the Hyper-Chem 7.5 and BuildQSAR packages. Results. The calculation of a number of molecular descriptors (electronic, steric, geometric, energy) was performed for 15 new polysubstituted functionalized aminothiazoles, with established in vivo antihypertensive activity. According to the calculated molecular descriptors and antihypertensive activity parameter, the QSAR models were derived НА = a + b ∙ X1 + c ∙ X2 + d ∙ X3 , where the activity parameter НА is antihypertensive activity and X1, X2, X3 are molecular descriptors. Conclusion. The study of ‘the structure - antihypertensive activity’ relationship for polysubstituted functionalized aminothiazoles was carried out. QSAR analysis revealed that volume, area, lipophilicity, dipole moment, refractivity, polarization of the molecule and energy of the lowest unoccupied molecular orbital have the most significant effect on antihypertensive activity. It was suggested that the attained QSAR-models may have antihypertensive activity within abovementioned row of compounds and can be considered as theoretical basis for de novo design of new potential antihypertensive drugs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Qsar-Analysis of Polysubstituted Functionalized Aminothiazoles With Antihypertensive Activity

Drapak

2020

IJMMR

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“…На основі in silico досліджень (фармакофорне моделювання, QSAR-аналіз, молекулярний докінг, прогнозування активності та токсичності) відібрано групу сполук, для яких здійснено цілеспрямований синтез і проведено первинний фармакологічний скринінг кардіотропних властивостей [5][6][7][8][9]. На основі отриманих результатів для поглиблених фармакологічних досліджень відібрано сполуку-лідер -[3-алліл-4-(4 1 -метоксифеніл)-3Н-тіазол-2-іліден]-(3 2 -трифлуорометилфеніл) Усі тварини, використані в експерименті, пройшли карантин, були адаптовані до лабораторного приміщення впродовж 7 діб і перебували на відповідному харчовому раціоні віварію.…”

Section: ключові слова: [3-алліл-4-(4 1метоксифеніл)-3н-тіазол-2-ілідunclassified

Синтез І Кардіотропна Дія [3-Алліл-4-(41-Метоксифеніл)-3н-Тіазол-2-Іліден](32-Трифлуорометилфеніл)аміну Гідроброміду В Білих Щурів

Drapak¹,

Серединська²,

Піняжко³

et al. 2019

Фармакологія та лікарська токсикологія

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У роботі наведено результати експериментального дослідження, присвяченого синтезу та вивченню кардіотропних властивостей оригінального похідного тіазолу – [3-алліл-4-(41-мето ксифеніл)-3Н-тіазол-2-іліден]-(32-трифлуорометилфеніл)аміну гідроброміду з умовною назвою Кардіазол, як перспективного вітчизняного кардіопротекторного лікарського засобу. Запропоновано зручний та ефективний метод отримання субстанції Кардіазолу, який придатний для промислових масштабів. У серії in vitro дослідів встановлено, що Кардіазол характеризується виразною кардіотропною дією, співмірною з мілдронатом. Встановлено, що за внутрішньоочеревинного введення білим щурам у дозі 7 мг/кг Кардіазол спричиняє гіпотензивний ефект і призводить до зниження артеріального тиску на 12,8 % і 16,7 % через 60 хв і 180 хв після введення, не впливає на частоту та ритм серцевих скорочень. Встановлено, що застосування Кардіазолу викликає кардіопротекторний ефект і спричиняє зниження рівня летальності білих щурів за адреналінової моделі інфаркту міокарда, покращує біохімічний профіль маркерів патологічного процесу (АСТ, ЛДГ, МВ-КФК) і нормалізує зміни на електрокардіограмі.

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“…This makes it possible to create a theoretical foundation for the development of directed synthesis of new biologically active substances and allows to avoid total pharmacological screening (Sachdeva S and Gupta S 2013, Makam et al 2013, Siddiqui N and Ahsan W 2010, Abdel-Maksoud et al 2015, Tehrani et al 2014. New biologically active substances with antihypertensive and cardiotropic activity among the 1,3-thiazole derivatives were found recently (Perekhoda et al 2017, Li-Min Duan et al 2014, Drapak et al 2019. Continuing research in this direction, we have modified the 1,3-thiazole ring by introducing pharmacophores, which potentially may affect the manifestation of the substance of cardiotropic activity.…”

Section: Introductionmentioning

confidence: 99%

Search for angiotensin II receptor antagonists among 4-aryl-n-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine derivatives

Drapak¹,

Zimenkovsky²,

Perekhoda³

et al. 2019

PHAR

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The aim of study was to find potential antihypertensive and cardiotropic drugs among new 4-aryl-N-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imines. Materials and methods: The target compounds were synthesized by condensation asymmetrical substituted thioureas with α-bromo-4-R1-acetophenones in ethanol medium. The structure and purity of the compounds synthesized were confirmed by 1H, 13C NMR-spectroscopy and elemental analysis. Docking studies of synthesized compounds to the active site of angiotensin receptor ІІ (PDB ID: 3R8A) were performed in order to find its potential inhibitors and to select promising compounds for experimental screening. Pharmacological studies of the influence on the cardiovascular system were performed. Results: The results of docking studies indicate a high affinity of all tested substances to the selected biotarget. The thermodynamic probability of binding of synthesized substances to protein 3R8A was confirmed by negative values of scoring functions. Hydrobromide of 4-(4-methoxyphenyl)-N-phenyl-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine 3(1) and hydrobrmide of 4-(4-methoxyphenyl)-N-(4-bromphenyl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine 3(3), which have the highest negative values of scoring functions, are recommended for in vivo pharmacological studies. Based on a complete analysis of the geometric location of the synthesized compounds (ligands) in the active site of the angiotensin II receptor, it was found that the complexes are formed with the involvement of Nitrogen atom of imino group, the 1,3-thiazole ring, the phenyl and alkyl moieties of the molecule form hydrogen bonds, intermolecular electrostatic and donor-acceptor interactions. The conducted pharmacological studies of the influence on the cardiovascular system have allowed to confirm the presence of antihypertensive effect inherent in compounds of this series (except for compound 3(2)). The most effective antihypertensive effect, which is similar in duration and strength of the effect of valsartan, was the effect of compound 3(5). Conclusions: In order to expand the arsenal of biologically active substances of cardiotropic action a systematic series of new 4-aryl-N-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine derivatives were synthesized. The structure and purity of the compounds synthesized were confirmed by 1H, 13C NMR-spectroscopy and elemental analysis. Based on the results of docking studies using Autodock 4.2.6 software, selected compounds with the best affinity for protein biomes (PDB codes: 3R8A) are promising for experimental studies of hypotensive and cardiotropic activity. The most effective antihypertensive effect, which is similar in duration and strength of the effect of valsartan, was the effect of compound 3(5). A comparative analysis of the results of molecular docking and in vivo results suggests that there is a positive correlation between scoring protein inhibition and experimental data.

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Cardioprotective Activity of Some 2-Arylimino-1,3-Thiazole Derivatives

Cited by 12 publications

References 14 publications

Qsar-Analysis of Polysubstituted Functionalized Aminothiazoles With Antihypertensive Activity

Qsar-Analysis of Polysubstituted Functionalized Aminothiazoles With Antihypertensive Activity

Синтез І Кардіотропна Дія [3-Алліл-4-(41-Метоксифеніл)-3н-Тіазол-2-Іліден](32-Трифлуорометилфеніл)аміну Гідроброміду В Білих Щурів

Search for angiotensin II receptor antagonists among 4-aryl-n-(aryl)-3-(prop-2-en-1-yl)-2,3-dihydro-1,3-thiazol-2-imine derivatives

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