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Conjugation of Aspergillus flavipes Taxol with Porphyrin Increases the Anticancer Activity of Taxol and Ameliorates Its Cytotoxic Effects.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2020 Jan 09; Vol. 25 (2). Date of Electronic Publication: 2020 Jan 09. - Publication Year :
- 2020
-
Abstract
- Taxol is one of the potential anticancer drugs; however, the yield of Taxol and its cytotoxicity are common challenges. Thus, manipulating the Taxol biosynthetic pathway from endophytic fungi, in addition to chemical modification with biocompatible polymers, is the challenge. Four fungal isolates, namely, Aspergillus flavipes , A. terreus , A. flavus , and A. parasiticus, were selected from our previous study as potential Taxol producers, and their potency for Taxol production was evaluated in response to fluconazole and silver nitrate. A higher Taxol yield was reported in the cultures of A. flavipes (185 µg/L) and A. terreus (66 µg/L). With addition of fluconazole, the yield of Taxol was increased 1.8 and 1.2-fold for A. flavipes and A. terreus, respectively, confirming the inhibition of sterol biosynthesis and redirecting the geranyl phosphate pool to terpenoids synthesis. A significant inhibition of ergosterol biosynthesis by A. flavipes with addition of fluconazole was observed, correlating with the increase on Taxol yield. To increase the Taxol solubility and to reduce its cytotoxicity, Taxol was modified via chemical conjugation with porphyrin, and the degree of conjugation was checked from the Thin layer chromatography and UV spectral analysis. The antiproliferative activity of native and modified Taxol conjugates was evaluated; upon porphyrin conjugation, the activity of Taxol towards HepG2 was increased 1.5-fold, while its cytotoxicity to VERO cells was reduced 3-fold.
- Subjects :
- Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
Aspergillus chemistry
Chlorocebus aethiops
Hep G2 Cells
Humans
Paclitaxel chemical synthesis
Paclitaxel isolation & purification
Paclitaxel pharmacology
Porphyrins chemical synthesis
Porphyrins pharmacology
Vero Cells
Antineoplastic Agents chemistry
Cell Proliferation drug effects
Paclitaxel chemistry
Porphyrins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 25
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 31936458
- Full Text :
- https://doi.org/10.3390/molecules25020263