KFU. Card publication. 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

Form of presentation

Articles in international journals and collections

Year of publication

2023

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Authors, employees of KFU

Mironov Vladimir Fedorovich, author

Nemtarev Andrey Vladimirovich, author

Bibliographic description in the original language

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.

Annotation

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.

Keywords

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

The name of the journal

RSC MEDICINAL CHEMISTRY

URL

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

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

https://repository.kpfu.ru/eng/?p_id=306755&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Mironov Vladimir Fedorovich	ru_RU
dc.contributor.author	Nemtarev Andrey Vladimirovich	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/eng/?p_id=306755&p_lang=2	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	Articles in international journals and collections	ru_RU