| Autor: |
Tsepaeva, Olga V., Nemtarev, Andrey V., Pashirova, Tatiana N., Khokhlachev, Michail V., Lyubina, Anna P., Amerkhanova, Syumbelya K., Voloshina, Alexandra D., Mironov, Vladimir F. |
| Zdroj: |
MedChemComm; 2023, Vol. 14 Issue: 3 p454-469, 16p |
| Abstrakt: |
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 4ain the absence of betulin. TPP-hybrid conjugate 10with two pharmacophore fragments, betulin and oleic acid, has significant cytotoxicity toward a wide range of tumor cells. The lowest IC50of 10is 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. |
| Databáze: |
Supplemental Index |
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