We
report herein the design, synthesis, and biological investigation
of a series of novel Pt(IV) prodrugs with non-steroidal anti-inflammatory
drugs naproxen, diclofenac, and flurbiprofen, as well as these with
stearic acid in the axial position. Six Pt(IV) prodrugs 5–10 were designed, which showed superior antiproliferative activity
compared to cisplatin as well as an ability to overcome tumor cell
line resistance to cisplatin. By tuning the drug lipophilicity via
variation of the axial ligands, the most potent Pt(IV) prodrug 7 was obtained, with an enhanced cellular accumulation of
up to 153-fold that of cisplatin and nanomolar cytotoxicity both in
2D and 3D cell cultures. Pt2+ species were detected at
different depths of MCF-7 spheroids after incubation with Pt(IV) prodrugs
using a Pt-coated carbon nanoelectrode. Cisplatin accumulation in
vivo in the murine mammary EMT6 tumor tissue of BALB/c mice after
Pt(IV) prodrug injection was proved electrochemically as well. The
drug tolerance study on BALB/c mice showed good tolerance of 7 in doses up to 8 mg/kg.
Understanding the chemical structure of lignin in the plant phloem contributes to the systematics of lignins of various biological origins, as well as the development of plant biomass valorization. In this study, the structure of the lignin from birch phloem has been characterized using the combination of three analytical techniques, including 2D NMR, Py-GC/MS, and APPI-Orbitrap-HRMS. Due to the specifics of the phloem chemical composition, two lignin preparations were analyzed: a sample obtained as dioxane lignin (DL) by the Pepper’s method and DL obtained after preliminary alkaline hydrolysis of the phloem. The obtained results demonstrated that birch phloem lignin possesses a guaiacyl–syringyl (G-S) nature with a unit ratio of (S/G) 0.7–0.9 and a higher degree of condensation compared to xylem lignin. It was indicated that its macromolecules are constructed from β-aryl ethers followed by phenylcoumaran and resinol structures as well as terminal groups in the form of cinnamic aldehyde and dihydroconiferyl alcohol. The presence of fatty acids and flavonoids removed during alkaline treatment was established. Tandem mass spectrometry made it possible to demonstrate that the polyphenolic components are impurities and are not incorporated into the structure of lignin macromolecules. An important component of phloem lignin is lignin–carbohydrate complexes incorporating xylopyranose moieties.
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