Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties

The introduction of a switchable function into the structure of a bioactive compound can endow it with unique capabilities for regulating biological activity under the influence of various types of external stimuli, which makes such hybrid compounds promising objects for photopharmacology, targeted...

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Asıl Yazarlar:	Demidov, O. P., Демидов, О. П.
Materyal Türü:	Статья
Dil:	English
Baskı/Yayın Bilgisi:	2023
Konular:	β-estradiol Spiropyran Сytotoxicity Molecular switch Acidochromism Single-crystal X-ray analysis
Online Erişim:	https://dspace.ncfu.ru/handle/20.500.12258/23984
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id	ir-20.500.12258-23984
record_format	dspace
spelling	ir-20.500.12258-239842023-07-05T12:14:03Z Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties Demidov, O. P. Демидов, О. П. β-estradiol Spiropyran Сytotoxicity Molecular switch Acidochromism Single-crystal X-ray analysis The introduction of a switchable function into the structure of a bioactive compound can endow it with unique capabilities for regulating biological activity under the influence of various types of external stimuli, which makes such hybrid compounds promising objects for photopharmacology, targeted drug delivery and bio-imaging. This work is devoted to the synthesis and study of new spirocyclic derivatives of important human hormones—β-estradiol and estrone—possessing a wide range of biological activities. The obtained hybrid compounds represent an indoline spiropyrans family, a widely known class of organic photochromic compounds. The structure of the compounds was confirmed by 1H and 13C NMR, IR, HRMS and single-crystal X-ray analysis. The intermolecular interactions in the crystals of spiropyran (3) were defined by Hirshfeld surfaces and 2D fingerprint plots, which were successfully acquired from CrystalExplorer (v21.5). All target hybrids demonstrated pronounced activity in the visible region of the spectrum. The mechanisms of thermal isomerization processes of spiropyrans and their protonated merocyanine forms were studied by DFT methods, which revealed the energetic advantage of the protonation process with the formation of a β-cisoid CCCH conformer at the first stage and its further isomerization to more stable β-transoid forms. The proposed mechanism of acidochromic transformation was confirmed by the additional NMR study data that allowed for the detecting of the intermediate CCCH isomer. The study of the short-term cytotoxicity of new spirocyclic derivatives of estrogens and their 2-formyl-precursors was performed on the HeLa cell model. The precursors and spiropyrans differed in toxicity, suggesting their variable applicability in novel anti-cancer technologies. 2023-07-05T12:13:15Z 2023-07-05T12:13:15Z 2023 Статья Ozhogin, I.V., Pugachev, A.D., Makarova, N.I., Belanova, A.A., Kozlenko, A.S., Rostovtseva, I.A., Zolotukhin, P.V., Demidov, O.P., El-Sewify, I.M., Borodkin, G.S., Metelitsa, A.V., Lukyanov, B.S. Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties // Molecules. - 2023. - 28(9), art. no. 3866. - DOI: 10.3390/molecules28093866 http://hdl.handle.net/20.500.12258/23984 en Molecules application/pdf application/pdf
institution	СКФУ
collection	Репозиторий
language	English
topic	β-estradiol Spiropyran Сytotoxicity Molecular switch Acidochromism Single-crystal X-ray analysis
spellingShingle	β-estradiol Spiropyran Сytotoxicity Molecular switch Acidochromism Single-crystal X-ray analysis Demidov, O. P. Демидов, О. П. Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties
description	The introduction of a switchable function into the structure of a bioactive compound can endow it with unique capabilities for regulating biological activity under the influence of various types of external stimuli, which makes such hybrid compounds promising objects for photopharmacology, targeted drug delivery and bio-imaging. This work is devoted to the synthesis and study of new spirocyclic derivatives of important human hormones—β-estradiol and estrone—possessing a wide range of biological activities. The obtained hybrid compounds represent an indoline spiropyrans family, a widely known class of organic photochromic compounds. The structure of the compounds was confirmed by 1H and 13C NMR, IR, HRMS and single-crystal X-ray analysis. The intermolecular interactions in the crystals of spiropyran (3) were defined by Hirshfeld surfaces and 2D fingerprint plots, which were successfully acquired from CrystalExplorer (v21.5). All target hybrids demonstrated pronounced activity in the visible region of the spectrum. The mechanisms of thermal isomerization processes of spiropyrans and their protonated merocyanine forms were studied by DFT methods, which revealed the energetic advantage of the protonation process with the formation of a β-cisoid CCCH conformer at the first stage and its further isomerization to more stable β-transoid forms. The proposed mechanism of acidochromic transformation was confirmed by the additional NMR study data that allowed for the detecting of the intermediate CCCH isomer. The study of the short-term cytotoxicity of new spirocyclic derivatives of estrogens and their 2-formyl-precursors was performed on the HeLa cell model. The precursors and spiropyrans differed in toxicity, suggesting their variable applicability in novel anti-cancer technologies.
format	Статья
author	Demidov, O. P. Демидов, О. П.
author_facet	Demidov, O. P. Демидов, О. П.
author_sort	Demidov, O. P.
title	Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties
title_short	Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties
title_full	Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties
title_fullStr	Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties
title_full_unstemmed	Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties
title_sort	novel indoline spiropyrans based on human hormones β-estradiol and estrone: synthesis, structure, chromogenic and cytotoxic properties
publishDate	2023
url	https://dspace.ncfu.ru/handle/20.500.12258/23984
work_keys_str_mv	AT demidovop novelindolinespiropyransbasedonhumanhormonesbestradiolandestronesynthesisstructurechromogenicandcytotoxicproperties AT demidovop novelindolinespiropyransbasedonhumanhormonesbestradiolandestronesynthesisstructurechromogenicandcytotoxicproperties
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Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties

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