КФУ. Карточка публикации. Novel triphenylphosphonium amphiphilic conjugates of glycerolipid type: synthesis, cytotoxic and antibacterial activity, targeted cancer-cells delivery

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NOVEL TRIPHENYLPHOSPHONIUM AMPHIPHILIC CONJUGATES OF GLYCEROLIPID TYPE: SYNTHESIS, CYTOTOXIC AND ANTIBACTERIAL ACTIVITY, TARGETED CANCER-CELLS DELIVERY

Форма представления

Статьи в зарубежных журналах и сборниках

Год публикации

2023

Язык

английский

Авторы, сотрудники КФУ

Миронов Владимир Федорович, автор

Немтарев Андрей Владимирович, автор

Библиографическое описание на языке оригинала

O.V.Tsepaeva, A.V.Nemtarev, T.N.Pashirova, M.V.Khokhlachev, A.P.Lyubina, S.K. Amerkhanova, A.D.Voloshina, V.F.Mironov. Novel triphenylphosphonium amphiphilic conjugates of glycerolipid type: synthesis, cytotoxic and antibacterial activity, targeted cancer-cells delivery. // RSC Med. Chem. 2023, 14(3), 454-469. Doi 10.1039/D2MD00363E.

Аннотация

This work deals with the creation of new cationic triphenylphosphonium amphiphilic conjugates of glycerolipid type (TPP-conjugates), bearing a pharmacophore terpenoid fragment (abietic acid and betulin) and a fatty acid residue in one hybrid molecule as a new generation of antitumor agents with high activity and selectivity. The TPP-conjugates showed high mitochondriotropy leading to the development of mitochondriotropic delivery systems such as TPP–pharmacosomes and TPP–solid lipid particles. Introducing the betulin fragment into the structure of a TPP-conjugate (compound 10) increases the cytotoxicity 3 times towards tumor cells of prostate adenocarcinoma DU-145 and 4 times towards breast carcinoma MCF-7 compared to TPP-conjugate 4a in the absence of betulin. TPP-hybrid conjugate 10 with two pharmacophore fragments, betulin and oleic acid, has significant cytotoxicity toward a wide range of tumor cells. The lowest IC50 of 10 is 0.3 μM toward HuTu-80. This is at the level of the reference drug doxorubicin. TPP–pharmacosomes (10/PC) increased the cytotoxic effect approximately 3 times toward HuTu-80 cells, providing high selectivity (SI = 480) compared to the normal liver cell line Chang liver.

Ключевые слова

triphenylphosphonium amphiphilic conjugates, mitochondriotropic delivery systems, targeted cancer-cells delivery

Название журнала

RSC MEDICINAL CHEMISTRY

URL

https://pubs.rsc.org/en/content/articlelanding/2023/md/d2md00363e

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https://repository.kpfu.ru/?p_id=306755

Полная запись метаданных

Поле DC	Значение	Язык
dc.contributor.author	Миронов Владимир Федорович	ru_RU
dc.contributor.author	Немтарев Андрей Владимирович	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	O.V.Tsepaeva, A.V.Nemtarev, T.N.Pashirova, M.V.Khokhlachev, A.P.Lyubina, S.K. Amerkhanova, A.D.Voloshina, V.F.Mironov. Novel triphenylphosphonium amphiphilic conjugates of glycerolipid type: synthesis, cytotoxic and antibacterial activity, targeted cancer-cells delivery. // RSC Med. Chem. 2023, 14(3), 454-469. Doi 10.1039/D2MD00363E.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/?p_id=306755	ru_RU
dc.description.abstract	RSC MEDICINAL CHEMISTRY	ru_RU
dc.description.abstract	This work deals with the creation of new cationic triphenylphosphonium amphiphilic conjugates of glycerolipid type (TPP-conjugates), bearing a pharmacophore terpenoid fragment (abietic acid and betulin) and a fatty acid residue in one hybrid molecule as a new generation of antitumor agents with high activity and selectivity. The TPP-conjugates showed high mitochondriotropy leading to the development of mitochondriotropic delivery systems such as TPP–pharmacosomes and TPP–solid lipid particles. Introducing the betulin fragment into the structure of a TPP-conjugate (compound 10) increases the cytotoxicity 3 times towards tumor cells of prostate adenocarcinoma DU-145 and 4 times towards breast carcinoma MCF-7 compared to TPP-conjugate 4a in the absence of betulin. TPP-hybrid conjugate 10 with two pharmacophore fragments, betulin and oleic acid, has significant cytotoxicity toward a wide range of tumor cells. The lowest IC50 of 10 is 0.3 μM toward HuTu-80. This is at the level of the reference drug doxorubicin. TPP–pharmacosomes (10/PC) increased the cytotoxic effect approximately 3 times toward HuTu-80 cells, providing high selectivity (SI = 480) compared to the normal liver cell line Chang liver.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	triphenylphosphonium amphiphilic conjugates	ru_RU
dc.subject	mitochondriotropic delivery systems	ru_RU
dc.subject	targeted cancer-cells delivery	ru_RU
dc.title	Novel triphenylphosphonium amphiphilic conjugates of glycerolipid type: synthesis, cytotoxic and antibacterial activity, targeted cancer-cells delivery	ru_RU
dc.type	Статьи в зарубежных журналах и сборниках	ru_RU