KFU. Card publication. Structural Analogs of Dehydrozingerone Containing a Pyridoxine Fragment Exhibit Membrane-Modulating Properties and Synergistically Enhance the Antitumor Activity of Cytostatics

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STRUCTURAL ANALOGS OF DEHYDROZINGERONE CONTAINING A PYRIDOXINE FRAGMENT EXHIBIT MEMBRANE-MODULATING PROPERTIES AND SYNERGISTICALLY ENHANCE THE ANTITUMOR ACTIVITY OF CYTOSTATICS

Form of presentation

Articles in Russian journals and collections

Year of publication

2023

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Authors, employees of KFU

Aymaletdinov Aleksandr Maazovich, author

Bondar Oksana Viktorovna, author

Kayumov Ayrat Rashitovich, author

Pavelev Roman Sergeevich, author

Pugachev Mikhail Vladimirovich, author

Shtyrlin Yuriy Grigorevich, author

Authors, postgraduates KFU

Karut Rauda , postgraduate kfu

Authors, students KFU

Mokhammad Taraa , author

Ygayev Beksultan Baktybekovich, author

Bibliographic description in the original language

.V. Bondar, R. Karwt, T. Mohammad, R.S. Pavelyev, M.V. Pugachev, Be.B. Ygaiev, A.R. Kayumov, A.M. Aimaletdinov, and Y.G. Shtyrlin. Structural Analogs of Dehydrozingerone Containing a Pyridoxine Fragment Exhibit Membrane-Modulating Properties and Synergistically Enhance the Antitumor Activity of Cytostatics // Russian Journal of Bioorganic Chemistry, 2023, 49 (4), P. 797-814. ISSN 1068-1620. DOI: 10.1134/S106816202304009X

Annotation

Previously we synthesized 10 novel structural analogs of dehydrozingerone based on the pyridoxine (vitamin B6) scaffold. Two lead compounds (compound (I) and compound (II)) expressed good cytotoxic activity against tumor cells and have shown higher selectivity than doxorubicin. In the present study, the mechanism of action of the leading analogues of dehydrozingerone, as well as the efficiency of their combinations with known cytostatics, was studied in more detail. We revealed a synergistic effect of leader dehydrozingerone analogs combinations with known cytostatics—doxorubicin, vinblastine and paclitaxel. It was established, that test compounds (I) and (II), as well as curcumin and dehydrozingerone, possess membranedamaging activity: cause cytoplasmic membrane depolarization and reduction in its microviscosity, which can explain the increase in toxicity of cytostatics. In addition, the test compounds were found to increase the ATPase activity of P-glycoproteins, likely acting as their substrates. It was also revealed that the test compounds increase the expression of BAX and E-cadherin, decrease the expression of Bcl-2 in cancer cells. Compound (I) does not cause blood cells hemolysis, does not possess DNA-damaging and mutagenic activity, and when administered intravenously to mice, the LD50 was 65 mg/kg. The investigated compounds are promising drug candidates to be further tested on animals with grafted tumors.

Keywords

pyridoxine, dehydrozingerone, curcumin, compositions with cytostatics, membrane-damaging activity

The name of the journal

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URL

https://link.springer.com/article/10.1134/S106816202304009X

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=292856&p_lang=2

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F_Finalnaya_versiya_stati_s_nomerami_stranic.pdf	1,75	pdf	show / download

Full metadata record

Field DC	Value	Language
dc.contributor.author	Aymaletdinov Aleksandr Maazovich	ru_RU
dc.contributor.author	Bondar Oksana Viktorovna	ru_RU
dc.contributor.author	Kayumov Ayrat Rashitovich	ru_RU
dc.contributor.author	Pavelev Roman Sergeevich	ru_RU
dc.contributor.author	Pugachev Mikhail Vladimirovich	ru_RU
dc.contributor.author	Shtyrlin Yuriy Grigorevich	ru_RU
dc.contributor.author	Mokhammad Taraa	ru_RU
dc.contributor.author	Ygayev Beksultan Baktybekovich	ru_RU
dc.contributor.author	Karut Rauda	ru_RU
dc.date.accessioned	2023-01-01T00:00:00Z	ru_RU
dc.date.available	2023-01-01T00:00:00Z	ru_RU
dc.date.issued	2023	ru_RU
dc.identifier.citation	.V. Bondar, R. Karwt, T. Mohammad, R.S. Pavelyev, M.V. Pugachev, Be.B. Ygaiev, A.R. Kayumov, A.M. Aimaletdinov, and Y.G. Shtyrlin. Structural Analogs of Dehydrozingerone Containing a Pyridoxine Fragment Exhibit Membrane-Modulating Properties and Synergistically Enhance the Antitumor Activity of Cytostatics // Russian Journal of Bioorganic Chemistry, 2023, 49 (4), P. 797-814. ISSN 1068-1620. DOI: 10.1134/S106816202304009X	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=292856&p_lang=2	ru_RU
dc.description.abstract	��	ru_RU
dc.description.abstract	Previously we synthesized 10 novel structural analogs of dehydrozingerone based on the pyridoxine (vitamin B6) scaffold. Two lead compounds (compound (I) and compound (II)) expressed good cytotoxic activity against tumor cells and have shown higher selectivity than doxorubicin. In the present study, the mechanism of action of the leading analogues of dehydrozingerone, as well as the efficiency of their combinations with known cytostatics, was studied in more detail. We revealed a synergistic effect of leader dehydrozingerone analogs combinations with known cytostatics—doxorubicin, vinblastine and paclitaxel. It was established, that test compounds (I) and (II), as well as curcumin and dehydrozingerone, possess membranedamaging activity: cause cytoplasmic membrane depolarization and reduction in its microviscosity, which can explain the increase in toxicity of cytostatics. In addition, the test compounds were found to increase the ATPase activity of P-glycoproteins, likely acting as their substrates. It was also revealed that the test compounds increase the expression of BAX and E-cadherin, decrease the expression of Bcl-2 in cancer cells. Compound (I) does not cause blood cells hemolysis, does not possess DNA-damaging and mutagenic activity, and when administered intravenously to mice, the LD50 was 65 mg/kg. The investigated compounds are promising drug candidates to be further tested on animals with grafted tumors.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	pyridoxine	ru_RU
dc.subject	dehydrozingerone	ru_RU
dc.subject	curcumin	ru_RU
dc.subject	compositions with cytostatics	ru_RU
dc.subject	membrane-damaging activity	ru_RU
dc.title	Structural Analogs of Dehydrozingerone Containing a Pyridoxine Fragment Exhibit Membrane-Modulating Properties and Synergistically Enhance the Antitumor Activity of Cytostatics	ru_RU
dc.type	Articles in Russian journals and collections	ru_RU