Molecules (Basel, Switzerland), 2022-01, Vol.27 (2), p.471
2022
Details
- Autor(en) / Beteiligte
- Titel
- Synthesis and Biological Investigation of Bile Acid-Paclitaxel Hybrids
- Ist Teil von
- Molecules (Basel, Switzerland), 2022-01, Vol.27 (2), p.471
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1420-3049eISSN: 1420-3049DOI: 10.3390/molecules27020471Titel-ID: cdi_doaj_primary_oai_doaj_org_article_1c36930ecea9485f9412a96da63b2339
- Format
- –
- Schlagworte
- Acids, Animals, Antineoplastic Agents, Phytogenic - chemical synthesis, Antineoplastic Agents, Phytogenic - chemistry, Antineoplastic Agents, Phytogenic - pharmacology, Antitumor activity, Apoptosis, Apoptosis - drug effects, Bile, bile acids, Bile Acids and Salts - chemical synthesis, Bile Acids and Salts - chemistry, Bile Acids and Salts - pharmacology, Bioavailability, Biological activity, Cancer therapies, Cell culture, Cell Line, Cell Survival - drug effects, Chenodeoxycholic acid, chenodeoxycholic acid conjugation, Chromatography, Colon, Colonic Neoplasms - drug therapy, Conjugation, Cytotoxicity, Deoxycholic Acid - analogs & derivatives, Deoxycholic Acid - chemical synthesis, Deoxycholic Acid - chemistry, Deoxycholic Acid - pharmacology, Drugs, Flow cytometry, Fluorescence, Fluorides, Humans, Hybrids, hybrids drugs, Leukemia - drug therapy, Mice, pacific blue, Paclitaxel, Paclitaxel - analogs & derivatives, Paclitaxel - chemical synthesis, Paclitaxel - chemistry, Paclitaxel - pharmacology, Tumor cell lines, Tumor cells, Ursodeoxycholic acid