The N-termini of the constitutional isomeric ferrocene peptides Boc–NH–Fn–CO–Ala–OMe (1) and Boc–Ala–NH–Fn–COOMe (2) were deprotected in the acidic milieu and subjected to oxalyl chloride-mediated ...dimerization to afford the oxalamides −(CO–NH–Fn–CO–Ala–OMe)2 (3) and −(CO–Ala–NH–Fn–COOMe)2 (4), respectively. The goal compounds were evaluated for their conformational properties, toluene gelation ability, and effect on cell viability of tumor (HeLa, MCF7, HepG2) and normal (HEK293T) cell lines. Detailed spectroscopic analysis in solution revealed the different conformational behavior of constitutional isomers 3 and 4, and oxalamide 3 was found to have a higher degree of chiral organization due to its involvement in stronger intramolecular hydrogen bonds. Crystallographic analysis showed the presence of two symmetry-independent conformers of compound 3 stabilized by stronger intramolecular hydrogen bonds. The tested compounds self-assemble in toluene to provide supramolecular nanostructures but were unable to form a stable gel. Interestingly, the formation of a stable gel was observed when the toluene solution of 4 was sonicated. Cytotoxic evaluation of 3 and 4 revealed a weaker growth-inhibitory effect on tumor cell lines compared to cisplatin. Oxalamide 3 appeared to be more cytotoxic to HeLa and MCF7 cancer cell lines than to normal HEK293T cells, indicating its potential for drug development as an anticancer agent.
Novel organometallic sugar amino acid conjugates 1–5 have been prepared by amide coupling of O-protected N-acetylmuramic acid and iso-muramic acid ...(2-3-amino-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yloxypropanoic acid) with 1-aminoferrocene, 1-aminoferrocene-1′-carboxylic acid (H-Fca-OH), or 1,1′-diaminoferrocene, respectively. The influence of the ferrocenyl moiety and presence of additional remote potential hydrogen atom acceptors and donors at the ferrocenyl core on the conformation and lipophilicity is investigated by TLC, IR, NMR, and CD spectroscopic methods augmented by density functional calculations. Furthermore, the redox potential of the ferrocene/ferrocenium couple is tuned by the electron-withdrawing and -donating nature of the substituents at the ferrocenyl label.
The emergence of COVID-19 has caused worldwide concern due to its high infectivity and mortality. Research groups around the world have prioritised drug development against COVID-19. Repurposing of ...already approved drugs, including the antimalarial drug chloroquine, has attracted considerable attention. The aim of this article is to (i) provide an overview of the recent chemical methods used to synthesise chloroquine and hydroxychloroquine, and (ii) provide insight into the data collected in 2020 on their efficacy against COVID-19. Unfortunately, the promising early results have not been confirmed and a clear and unambiguous conclusion on their clinical efficacy has not yet been drawn.
The development of turn-based inhibitors of protein-protein interactions has attracted considerable attention in medicinal chemistry. Our group has synthesized a series of peptides derived from an ...amino-functionalized ferrocene to investigate their potential to mimic protein turn structures. Detailed DFT and spectroscopic studies (IR, NMR, CD) have shown that, for peptides, the backbone chirality and bulkiness of the amino acid side chains determine the hydrogen-bond pattern, allowing tuning of the size of the preferred hydrogen-bonded ring in turn-folded structures. However, their biological potential is more dependent on their lipophilicity. In addition, our pioneering work on the chiroptical properties of aminoferrocene-containing peptides enables the correlation of their geometry with the sign of the CD signal in the absorption region of the ferrocene chromophore. These studies have opened up the possibility of using aminoferrocene and its derivatives as chirooptical probes for the determination of various chirality elements, such as the central chirality of amino acids and the helicity of peptide sequences.
The unnatural organometallic amino acid 1'-aminoferrocene-1-carboxylic acid (Fca) induces a turn structure in a tetrapeptide with anti-parallel strands which is stabilized by two intra-molecular ...hydrogen bonds in the solid state and in solution.
The concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The ...peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more active and selective than natural peptides and have fewer side effects. One of the synthetic strategies for obtaining peptidomimetics involves mimicking peptide α-helices, β-sheets or turns. Turns are usually located on the protein surface where they interact with various receptors and are therefore involved in numerous biological events. Among the various synthetic tools for turn mimetic design reported so far, our group uses an approach based on the insertion of different ferrocene templates into the peptide backbone that both induce turn formation and reduce conformational flexibility. Here, we conjugated methyl 1'-aminoferrocene-carboxylate with homo- and heterochiral Pro-Ala dipeptides to investigate the turn formation potential and antiproliferative properties of the resulting peptidomimetics
-
. Detailed spectroscopic (IR, NMR, CD), X-ray and DFT studies showed that the heterochiral conjugates
and
were more suitable for the formation of β-turns. Cell viability study, clonogenic assay and cell death analysis showed the highest biological potential of homochiral peptide
.
Considering the enormous importance of protein turns as participants in various biological events, such as protein–protein interactions, great efforts have been made to develop their conformationally ...and proteolytically stable mimetics. Ferrocene-1,1′-diamine was previously shown to nucleate the stable turn structures in peptides prepared by conjugation with Ala (III) and Ala–Pro (VI). Here, we prepared the homochiral conjugates of ferrocene-1,1′-diamine with l-/d-Phe (32/35), l-/d-Val (33/36), and l-/d-Leu (34/37) to investigate (1) whether the organometallic template induces the turn structure upon conjugation with amino acids, and (2) whether the bulky or branched side chains of Phe, Val, and Leu affect hydrogen bonding. Detailed spectroscopic (IR, NMR, CD), X-ray, and DFT studies revealed the presence of two simultaneous 10-membered interstrand hydrogen bonds, i.e., two simultaneous β-turns in goal compounds. A preliminary biological evaluation of d-Leu conjugate 37 showed its modest potential to induce cell cycle arrest in the G0/G1 phase in the HeLa cell line but these results need further investigation.
This research underlines the potential of employing emulsion/internal gelation encapsulation in alginate and pectin hydrogels for the simultaneous delivery of hydrophilic (polyphenols from dandelion ...(Taraxacum officinalis L.) extract) and lypophilic (β-carotene) compounds. The approach of reinforcing alginate and pectin hydrogels by whey proteins and hydroxypropyl methylcellulose (HPMC) as the carriers for the design of microencapsulated delivery systems was also evaluated. Comprehensive characterization of the morphological properties, particle size, encapsulation efficiency, interactions and release in gastrointestinal conditions was achieved. A simple and effective procedure based on the ionic gelation of emulsions for microencapsulation of polyphenols and β-carotene was developed, allowing formulation of micro-sized particles ranging ≤800 μm, which retained their spherical morphological properties upon drying. Incorporation of whey proteins and HPMC in the alginate gel contributed to better encapsulation parameters i.e. the morphological properties and encapsulation efficiency in relation to plain alginate particles. The combination of alginate with whey proteins as the carrier matrix arised as the optimal delivery system, owing to its regular, spherical shape, high encapsulation efficiency of total polyphenols (77,35%) and very good retention of hydroxycinnamic acids (89,14%), while the binary mixture of alginate and HPMC as the carrier enabled the best (prolongued) release profile of these compounds from the formulated microparticles in simulated gastrointestinal fluids.
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•Microencapsulation procedure by ionic gelation of emulsions established.•Simultaneous entrappment of polyphenols and ß-carotene achieved.•Reinforcement with whey proteins preserved microbead’s spherical properties.•Higher encapsulation efficiency of hydroxycinnamic acids observed.•Alginate in combination with whey proteins - the optimal carrier system.
The aim of the present study was to examine changes in phenolic compounds during refining of rapeseed oil. In crude rapeseed oil, 4-vinylsyringol (canolol) is the dominant phenolic compound, ...accounting for 85% of total phenolics. Refining decreased the total amount of phenolic compounds by 90%. NMR and MS analyses of edible rapeseed oil phenolic extracts identified 4-vinylsyringol dimer as the dominant phenolic compound. This phenolic compound appears to form through acid-catalyzed dimerization-aromatic substitution of 4-vinylsyringol monomers. Analysis of rapeseed oils from different stages of the refining process suggest that 4-vinylsyringol dimer forms during the neutralization phase, when H3PO4 acts as a catalyst, or during bleaching, when acid-activated bleaching earth acts as the catalyst. Whether 4-vinylsyringol forms during one or the other phase appears to depend on the phospholipid content of the crude oil. These insights may be useful for designing rapeseed oil refining processes that maximize levels of 4-vinylsyringol dimer.
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