Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC₅₀ of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC₅₀ of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.     

Deep Eutectic Solvents: Alternative Solvents for Biomass-Based Waste Valorization

Innovative technologies can transform what are now considered “waste streams” into feedstocks for a range of products. Indeed, the use of biomass as a source of biopolymers and chemicals currently has a consolidated economic dimension, with well-developed and regulated markets, in which the evaluation of the manufacturing processes relies on specific criteria such as purity and yield, and respects defined regulatory parameters for the process safety. In this context, ionic liquids and deep eutectic solvents have been proposed as environmentally friendly solvents for applications related to biomass waste valorization. This mini-review draws attention to some recent advancements in the use of a series of new-solvent technologies, with an emphasis on deep eutectic solvents (DESs) as key players in the development of new processes for biomass waste valorization. This work aims to highlight the role and importance of DESs in the following three strategic areas: chitin recovery from biomass and isolation of valuable chemicals and biofuels from biomass waste streams.     

Poly(ε-caprolactone)-Based Graft Copolymers: Synthesis Methods and Applications in the Biomedical Field: A Review

Synthetic biopolymers are attractive alternatives to biobased polymers, especially because they rarely induce an immune response in a living organism. Poly ε-caprolactone (PCL) is a well-known synthetic aliphatic polyester universally used for many applications, including biomedical and environmental ones. Unlike poly lactic acid (PLA), PCL has no chiral atoms, and it is impossible to play with the stereochemistry to modify its properties. To expand the range of applications for PCL, researchers have investigated the possibility of grafting polymer chains onto the PCL backbone. As the PCL backbone is not functionalized, it must be first functionalized in order to be able to graft reactive groups onto the PCL chain. These reactive groups will then allow the grafting of new reagents and especially new polymer chains. Grafting of polymer chains is mainly carried out by “grafting from” or “grafting onto” methods. In this review we describe the main structures of the graft copolymers produced, their different synthesis methods, and their main characteristics and applications, mainly in the biomedical field.     

Push-Pull Structures Based on 2-Aryl/thienyl Substituted Quinazolin-4(3H)-ones and 4-Cyanoquinazolines

Design and synthesis of 2-(aryl/thiophen-2-yl)quinazolin-4(3H)-ones and 4-cyano-2-arylquinazolines with Et₂N-, Ph₂N- or carbazol-9-yl- electron donating fragment are described. The key photophysical properties of these compounds have been studied by UV/Vis absorption and fluorescence spectroscopy in solvents of different polarity (toluene and MeCN). 2-(Aryl/thiophen-2-yl)quinazolin-4(3H)-ones show fluorescence in blue-green region in toluene solution with quantum yields up to 89% in the case of 2-(4’-N,N-diphenylamino[1,1’-biphenyl]-4-yl)-quinazolin-4(3H)-one. Moreover, triphenylamino derivative based on quinazolin-4(3H)-one with para-phenylene linker displays the highest quantum yield of 40% in powder. The fluorescence QY of Et₂N and Ph₂N derivatives decrease when going from toluene to MeCN solution, whereas carbazol-9-yl counterparts demonstrate strengthening of intensity that emphasizes the strong influence of donor fragment nature on photophysical properties. 4-Cyanoquinazolines are less emissive in both solvents, as well as, in solid state. The introduction of cyano group into position 4 leads to orange/red colored powder and dual emission bands. Some molecules demonstrate the increase in emission intensity upon addition of water to MeCN solution. According to frontier molecular orbitals (HOMO, LUMO) calculations, the energy gap of 4-cyanoquinazoline decreases by more than 1 eV compared to quinazolin-4-one, that is consistent with experimental data.     

1,4-Naphthoquinone Motif in the Synthesis of New Thiopyrano[2,3-d]thiazoles as Potential Biologically Active Compounds

A series of 11-substituted 3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones were obtained via hetero-Diels-Alder reaction of 5-alkyl/arylallylidene/-4-thioxo-2-thiazolidinones and 1,4-naphthoquinones. The structures of newly synthesized compounds were established by spectral data and a single-crystal X-ray diffraction analysis. According to U.S. NCI protocols, compounds 3.5 and 3.6 were screened for their anticancer activity; 11-Phenethyl-3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d]thiazole-2,5,10-trione (3.6) showed pronounced cytotoxic effect on leukemia (Jurkat, THP-1), epidermoid (KB3-1, KBC-1), and colon (HCT116wt, HCT116 p53-/-) cell lines. The cytotoxic action of 3.6 on p53-deficient colon carcinoma cells was two times weaker than on HCT116wt, and it may be an interesting feature of the mechanism action.     

Effect of Microwave Plasma Pre-Treatment on Cotton Cellulose Dissolution

The utilization of cellulose to its full potential is constrained by its recalcitrance to dissolution resulting from the rigidity of polymeric chains, high crystallinity, high molecular weight, and extensive intra- and intermolecular hydrogen bonding network. Therefore, pretreatment of cellulose is usually considered as a step that can help facilitate its dissolution. We investigated the use of microwave oxygen plasma as a pre-treatment strategy to enhance the dissolution of cotton fibers in aqueous NaOH/Urea solution, which is considered to be a greener solvent system compared to others. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, and Powder X-ray Diffraction analyses revealed that plasma pretreatment of cotton cellulose leads to physicochemical changes of cotton fibers. Pretreatment of cotton cellulose with oxygen plasma for 20 and 40 min resulted in the reduction of the molecular weight of cellulose by 36% and 60% and crystallinity by 16% and 25%, respectively. This reduction in molecular weight and crystallinity led to a 34% and 68% increase in the dissolution of 1% (w/v) cotton cellulose in NaOH/Urea solvent system. Thus, treating cotton cellulose with microwave oxygen plasma alters its physicochemical properties and enhanced its dissolution.     

Achillea moschata Wulfen: From Ethnobotany to Phytochemistry,Morphology, and Biological Activity

A multidisciplinary investigation on Achillea moschata Wulfen (Asteraceae) is outlined herein. This work, part of the European Interreg Italy–Switzerland B-ICE project, originated from an ethnobotanical survey performed in Chiesa in Valmalenco (Sondrio, Lombardy, Northern Italy) in 2019–2021 which highlighted this species’ relevance of use in folk medicine to treat gastrointestinal diseases. In addition, this contribution included analyses of the: (a) phytochemical profile of the aqueous and methanolic extracts of the dried flower heads using LC-MS/MS; (b) morpho-anatomy and histochemistry of the vegetative and reproductive organs through Light, Fluorescence, and Scanning Electron Microscopy; (c) biological activity of the aqueous extract concerning the antioxidant and anti-inflammatory potential through cell-based in vitro models. A total of 31 compounds (5 phenolic acids, 13 flavonols, and 13 flavones) were detected, 28 of which included in both extracts. Covering and secreting trichomes were observed: the biseriate 10-celled glandular trichomes prevailing on the inflorescences represented the main sites of synthesis of the polyphenols and flavonoids detected in the extracts, along with volatile terpenoids. Finally, significant antioxidant and anti-inflammatory activities of the aqueous extract were documented, even at very low concentrations; for the first time, the in vitro tests allowed us to formulate hypotheses about the mechanism of action. This work brings an element of novelty due to the faithful reproduction of the traditional aqueous preparation and the combination of phytochemical and micromorphological research approaches.     

Ligand-free nickel catalyzed perfluoroalkylation of arenes and heteroarenes

We describe a “ligand-free” Ni-catalyzed perfluoroalkylation of heteroarenes to produce a diverse array of trfiluoromethyl, pentafluoroethyl and heptafluoropropyl adducts. Catalysis proceeds at room temperature via a radical pathway. The catalytic protocol is distinguished by its simplicity, and its wide scope demonstrates the potential in the late-stage functionalization of drug analogues and peptides.

A ligand-free, room temperature, Ni-catalyzed perfluoroalkylation of heteroarenes produced a diverse array of polyfluorinated adducts; potential in the late-stage functionalization of drugs and peptides is also demonstrated.     

Novel C60 Fullerenol-Gentamicin Conjugate–Physicochemical Characterization and Evaluation of Antibacterial and Cytotoxic Properties

This study aimed to develop, characterize, and evaluate antibacterial and cytotoxic properties of novel fullerene derivative composed of C₆₀ fullerenol and standard aminoglycoside antibiotic–gentamicin (C₆₀ fullerenol-gentamicin conjugate). The successful introduction of gentamicin to fullerenol was confirmed by X-ray photoelectron spectroscopy which together with thermogravimetric and spectroscopic analysis revealing the formula of the composition as C₆₀(OH)₁₂(GLYMO)₁₁(Gentamicin)_0.8. The dynamic light scattering (DLS) revealed that conjugate possessed ability to form agglomerates in water (size around 115 nm), while Zeta potential measurements demonstrated that such agglomerates possessed neutral character. In vitro biological assays indicated that obtained C₆₀ fullerenol-gentamicin conjugate possessed the same antibacterial activity as standard gentamicin against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli, which proves that combination of fullerenol with gentamicin does not cause the loss of antibacterial activity of antibiotic. Moreover, cytotoxicity assessment demonstrated that obtained fullerenol-gentamicin derivative did not decrease viability of normal human fibroblasts (model eukaryotic cells) compared to control fibroblasts. Thus, taking into account all of the results, it can be stated that this research presents effective method to fabricate C₆₀ fullerenol-gentamicin conjugate and proves that such derivative possesses desired antibacterial properties without unfavorable cytotoxic effects towards eukaryotic cells in vitro. These promising preliminary results indicate that obtained C₆₀ fullerenol-gentamicin conjugate could have biomedical potential. It may be presumed that obtained fullerenol may be used as an effective carrier for antibiotic, and developed fullerenol-gentamicin conjugate may be apply locally (i.e., at the wound site). Moreover, in future we will evaluate possibility of its applications in inter alia tissue engineering, namely as a component of wound dressings and implantable biomaterials.     

Polysaccharides as Green Fuels for the Synthesis of MgO: Characterization and Evaluation of Antimicrobial Activities

The synthesis of structured MgO is reported using feedstock starch (route I), citrus pectin (route II), and Aloe vera (route III) leaf, which are suitable for use as green fuels due to their abundance, low cost, and non-toxicity. The oxides formed showed high porosity and were evaluated as antimicrobial agents. The samples were characterized by energy-dispersive X-ray fluorescence (EDXRF), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The crystalline periclase monophase of the MgO was identified for all samples. The SEM analyses show that the sample morphology depends on the organic fuel used during the synthesis. The antibacterial activity of the MgO-St (starch), MgO-CP (citrus pectin), and MgO-Av (Aloe vera) oxides was evaluated against pathogens Staphylococcus aureus (ATCC 6538P) and Escherichia coli (ATCC 8739). Antifungal activity was also studied against Candida albicans (ATCC 64548). The studies were carried out using the qualitative agar disk diffusion method and quantitative minimum inhibitory concentration (MIC) tests. The MIC of each sample showed the same inhibitory concentration of 400 µg. mL⁻¹ for the studied microorganisms. The formation of inhibition zones and the MIC values in the antimicrobial analysis indicate the effective antimicrobial activity of the samples against the test microorganisms.