Conjugation of Aspergillus flavipes Taxol with Porphyrin Increases the Anticancer Activity of Taxol and Ameliorates Its Cytotoxic Effects

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.

Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation

“…Thus, Taxol was considered as one of the most important additions to the chemotherapeutic field in the late 20th century. The chronology of Taxol discovery, development and its clinical trials has been documented [ 23 , 30 , 32 , 33 , 34 ]. In the late 1980s, diterpenoid Taxane or Taxoid derivatives, Taxol and Docetaxel were introduced and proved to be effective in treatment of a variety of solid tumors including ovarian, lung, breast and bladder cancers [ 35 ].…”

“…So many natural compounds are reported to use as antibiotics, anticancer agents. Many endophytic fungi isolated from different medicinal plants are reported to be main source of many secondary metabolites and pharmaceutical compounds with biotechnological roles [ 3 , 11 , 12 , 13 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 32 , 34 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 78 , 79 , 97 , 99 , 100 , 101 , 102 , 103 , 104 ]. Fusarubin and anhydrofusarubin, isolated from the Cladosporium species an endophyte of Rauwolfia serpentina , displayed a promising antimicrobial and antitumor activities [ 105 ].…”

Bioremediation and tolerance of zinc ions using Fusarium solani

“…The adaptation of fungi to metal stress caused the modifications of the cell surface that depended on the type and concentration of metal and thought to be associated with intracellular detoxification of heavy metals ( Kim et al., 2012 ; Luna et al., 2015 ). These changes refers to the formation of intracellular vacuoles that act as storage compartments for thiol-containing compounds that can bind metal ions and accumulate them in the vacuoles and hence increase the pressure within the mycelia leading to cell wall protrusions ( Paraszkiewicz et al., 2010 , Li et al., 2017 , Gururajan and Belur, 2018 , El-Sayed et al., 2020 a , b ).

Figure 1 SEM micrograph of growing F. solani (a) Zn(II)-free pellets (control), (b–e) Zn(II)-loaded pellets (9000 mg/l).

…”

Detection, Purification and Elucidation of Chemical Structure and Antiproliferative Activity of Taxol Produced by Penicillium chrysogenum

“…After running, they were examined using UV illumination at 227 nm (Min-UVIS, DESAGA, Heidelberg, Germany). In addition, the plates were sprayed with 1% vanillin in sulfuric acid ( w / v ) with gentle heating [ 48 , 49 ]. A bluish spot fading to dark grey was developed after 24 h, compared to authentic taxol (Sigma-Aldrich, Cat.…”

“…The purified taxol substance by HPLC from the above steps was subjected to instrumental analysis [ 48 , 49 , 50 , 51 , 52 ]. Fourier transform infrared (FTIR) and ultraviolet (UV) spectra of the suspected taxol molecule were carried out as described previously in the microanalytical center, Cairo University (Egypt) [ 13 , 53 ].…”