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A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used.

The imbalance between prooxidants and antioxidants in biological systems, known as oxidative stress, can lead to a disruption of redox signaling by the reactive oxygen/nitrogen species and is related to severe diseases. The most vulnerable moiety targeted by oxidant species in the redox signaling pathways is the thiol (SH) group in the cysteine residues, especially in its deprotonated (S−) form. Cysteine, along with its oxidized, disulfide-containing form, cystine, constitute one of the most abundant low molecular weight biological redox couples, providing a significant contribution to the redox homeostasis in living systems. In this work, NMR spectra from cysteine, cystine, and cysteine-containing small peptides were thoroughly studied at the submolecular level, and through the chemical shift data set of their certain atoms it is possible to estimate either thiolate basicity or the also related standard redox potential. Regression analysis demonstrated a strong linear relationship for chemical shift vs thiolate logK of the cysteine microspecies data. The αCH 13C chemical shift is the most promising estimator of the acid-base and redox character.

Several ecdysteroid acetonides act as adjuvant chemo-sensitizing agents against various cancer cell lines, and they can be formulated to self-assembling nanoparticle (NP) pro-drugs through a hydrolysable conjugation with squalene. In the bloodstream such squalenoylated nanoparticles dissolve into low-density lipoprotein (LDL) that allows targeting tissues containing high levels of LDL-receptors. In this work, ajugasterone C 2,3;20,22-diacetonide (3) and 11α-hydroxypoststerone 2,3-acetonide (4) were squalenoylated to obtain two new ecdysteroid pro-drugs (6 and 7) and their nano-assemblies (6NP and 7NP). A complete NMR signal assignment of 6 and 7 was achieved. Interaction of compounds 3 and 4 with chemotherapeutics was studied by the Chou-Talalay method. Compound 3 showed strong synergism with doxorubicin on a multi-drug resistant lymphoma cell line. In contrast, its nanoassembly 6NP significantly decreased the cytotoxicity of doxorubicin on these MDR cells, strongly suggesting that at least the 2,3-acetonide group was cleaved by the acidic pH of lysosomes after endocytosis of the prodrug. Further, compound 4 acted in strong antagonism with paclitaxel on MCF-7 cells and its nanoassemby 7NP also protected MCF-7 cells from the effect of paclitaxel. Our results suggest that acid-resistant A-ring substitution would be crucial to design adjuvant antitumor squalenoylated ecdysteroid prodrugs. Additionally, our results may be considered as a serendipitous discovery of a novel way to deliver cytoprotective, adaptogen ecdysteroids to healthy tissues with upregulated LDL-R.