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- Title
Synthesis and Biological Investigation of Bile Acid-Paclitaxel Hybrids.
- Authors
Melloni, Elisabetta; Marchesi, Elena; Preti, Lorenzo; Casciano, Fabio; Rimondi, Erika; Romani, Arianna; Secchiero, Paola; Navacchia, Maria Luisa; Perrone, Daniela
- Abstract
Chenodeoxycholic acid and ursodeoxycholic acid (CDCA and UDCA, respectively) have been conjugated with paclitaxel (PTX) anticancer drugs through a high-yield condensation reaction. Bile acid-PTX hybrids (BA-PTX) have been investigated for their pro-apoptotic activity towards a selection of cancer cell lines as well as healthy fibroblast cells. Chenodeoxycholic-PTX hybrid (CDC-PTX) displayed cytotoxicity and cytoselectivity similar to PTX, whereas ursodeoxycholic-PTX hybrid (UDC-PTX) displayed some anticancer activity only towards HCT116 colon carcinoma cells. Pacific Blue (PB) conjugated derivatives of CDC-PTX and UDC-PTX (CDC-PTX-PB and UDC-PTX-PB, respectively) were also prepared via a multistep synthesis for evaluating their ability to enter tumor cells. CDC-PTX-PB and UDC-PTX-PB flow cytometry clearly showed that both CDCA and UDCA conjugation to PTX improved its incoming into HCT116 cells, allowing the derivatives to enter the cells up to 99.9%, respect to 35% in the case of PTX. Mean fluorescence intensity analysis of cell populations treated with CDC-PTX-PB and UDC-PTX-PB also suggested that CDC-PTX-PB could have a greater ability to pass the plasmatic membrane than UDC-PTX-PB. Both hybrids showed significant lower toxicity with respect to PTX on the NIH-3T3 cell line.
- Subjects
CENTERS for Disease Control &; Prevention (U.S.); BIOSYNTHESIS; CHENODEOXYCHOLIC acid; URSODEOXYCHOLIC acid; ANTINEOPLASTIC agents; CELL populations
- Publication
Molecules, 2022, Vol 27, Issue 2, p471
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules27020471