Search Results (85)

With the continuous expansion of urban areas, the treatment of urban sewage is facing significant challenges. Tens of thousands of tons of municipal sludge (MS) are produced annually, which not only occupies substantial land resources but also poses potential environmental threats, thereby complicating wastewater treatment processes. Proper management of MS has thus become a critical issue requiring urgent attention. Meanwhile, water pollution continues to worsen, endangering both ecological systems and human health. MS contains a variety of organic compounds with active functional groups capable of forming strong coordination interactions with various waterborne pollutants. Building on this foundation, we successfully develop a multifunctional adsorbent using MS as the raw material through biomineralization. The synthesized adsorbent shows outstanding performance, exhibiting high adsorption capacity for fluoride (F⁻) and hexavalent uranium (U(VI)) in high-fluorine uranium-containing wastewater, effectively reducing the concentrations of these harmful substances. Additionally, the adsorbent shows strong affinity for the cationic dye methylene blue, making it highly suitable for the treatment of wastewater from the printing and dyeing industries. Notably, the adsorbent also possesses antibacterial properties, demonstrating significant bactericidal activity against Gram-negative E. coli in wastewater. The multifunctional adsorbent not only offers a novel solution to enhancing water quality and safety, but also represents a promising strategy for sustainable wastewater treatment. Full article

The use of dyes as sensitizing agents to increase semiconductor activity is a strategy already adopted in the field of heterogeneous photocatalysis, but the compounds applied are noble metal-based and sometimes difficult to synthesize, which make it more expensive. In this work, it was discovered that methylene blue can perform such an effect on an iron molybdate functionalized with peroxo groups on the surface. This material, called MoOxoFe, was tested together with its analogue MoFe (produced without H₂O₂ in the synthesis) in the degradation of methylene blue. The rapid degradation of the dye led to the hypothesis of sensitization, which was investigated and proven by additional photocatalytic tests with sensitized material, MoOxoFe-MB, and spectroscopies, such as EPR and XPS. Full article

Leukemia, one of the major causes of cancer death, ranks 11th worldwide among cancer-related deaths. The current treatment of leukemia faces challenges recently due to a high burden of side effects. It is well established that curcumin has anticancer and tumor-suppressing activities in several cancers in addition to leukemia. Accordingly, 15 derivatives were designed and prepared to improve the shortcomings of curcumin, such as poor aqueous solubility, chemical instability, and low bioavailability. All 15 were evaluated for cytotoxicity against the leukemic cell line MOLT-4, which led to the prioritization and further evaluation of compound curcuminoid (2E,5E)-2,5-bis((3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)cyclopentan-1-one 5i. 5i. Compared to curcumin, 5i was significantly more effective in inducing mitochondrial dysfunction in MOLT-4 cells; hence increased ROS production and cytotoxicity. Treatment groups showed change in mitochondrial membrane potential by flow cytometry analysis. Moreover, tumor volume reduction observed with 5i treatment in Dalton’s Lymphoma model was accompanied with low toxicity. Intrinsic pathways of apoptosis was initiated by compound 5i that lowered Bcl-2 expression while augmenting cytochrome c, Bak and Bax levels both in vivo and in vitro. These results showcase the potent antiproliferative as well as cytotoxic effects of 5i at nanomolar doses against leukemia being at least 60 times more effective than curcumin. Full article

Background: Paullinia cupana Kunth, popularly known as guarana, a native Amazonian shrub cultivated by the Sateré-Mawé ethnic group, has been used in traditional medicine for various purposes, including stimulant and therapeutic actions, due to its chemical composition, which is rich in bioactive compounds. This study explored the reductive potential of guarana with nanobiotechnology and aimed to synthesize silver nanoparticles (AgNPs) using the aqueous extract of leaves collected during the dry and rainy seasons, assessing their biological and catalytic activities. Methods: The AgNPs were synthesized in a water bath at 70 °C for three hours and then characterized using techniques such as UV-Vis spectroscopy, DLS, zeta potential, MET, NTA, and EDX and had their effects on various biological systems assessed in vitro, as well as in catalytic tests aimed at indicating the probable influence of the time when the plant material was collected on the properties of the nanostructures. Results: The AgNPs had an average diameter between 39.33 and 126.2 nm, spherical morphology, absorption bands between 410 and 450 nm, and high colloidal stability over two years. The biological results showed antibacterial activity against all the species tested, as well as remarkable antioxidant action against DPPH and ABTS free radicals, in the same way as the aqueous leaf extracts of P. cupana, in addition to cytotoxic properties against cancerous (A431 and A549) and non-cancerous (HaCaT and HNTMC) cells. The AgNPs were active against promastigote forms of Leishmania (Leishmania) amazonensis while not affecting the viability of macrophages, and from the LC₅₀ and LC₉₀ values, the AgNPs were more effective than the metal salt solution in controlling Aedes aegypti larvae and pupae. We also reported that the catalytic degradation of the organic dyes methylene blue (MB) and methyl orange (MO) by AgNPs was over 90% after 40 or 14 min, respectively. Conclusions: Thus, our results support the potential of seasonal extracts of guarana leaves to produce AgNPs with diverse application possibilities for the health, industrial, and environmental sectors. Full article

Background: Methylenebisphosphonic derivatives including hydroxy-methylenebisphosphonic species may be of potential biological activity, and a part of them is used in the treatment of bone diseases. Methods: Methylenebisphosphonates may be obtained by the Michaelis–Arbuzov reaction of suitably α-substituted methylphosphonates and trialkyl phosphites or phosphinous esters, while the hydroxy-methylene variations are prepared by the Pudovik reaction of α-oxophosphonates and different >P(O)H reagents, such as diethyl phosphite and diarylphosphine oxides. Results: After converting α-hydroxy-benzylphosphonates and -phosphine oxides to the α-halogeno- and α-sulfonyloxy derivatives, they were utilized in the Michaelis–Arbuzov reaction with trialkyl phosphites and ethyl diphenylphosphinite to afford the corresponding bisphosphonate, bis(phosphine oxide) and phosphonate–phosphine oxide derivatives. The Pudovik approach led to α-hydroxy-methylenebisphosphonic species and to their rearranged products. A part of the derivatives revealed a significant cytotoxic effect on pancreatic adenocarcinoma or multiple myeloma cells. Conclusions: The new families of compounds synthesized by our novel approaches may be of practical importance due to the significant cytotoxic activity on the cell cultures investigated. Compounds lacking hydroxy groups showed anti-myeloma activity or limited effect on pancreatic cancer (PANC-1) cells unless substituted with para-trifluoromethyl group. Hydroxy-containing bisphosphonates and their rearranged derivatives demonstrated varying effects depending on structural modifications. While myeloma (U266) cells indicated greater sensitivity overall, the most significant reductions in cell viability were observed in PANC-1 cancer cells, raising potential therapeutic applications of bisphosphonates beyond myeloma-associated bone disease, particularly for malignancies like pancreatic ductal adenocarcinoma. Full article

The synthesis of phosphorous indenoquinolines and their biological evaluation as topoisomerase 1 (TOP1) inhibitors and antiproliferative agents were performed. First, the preparation of new hybrid 5H-indeno[2,1-c]quinolines with a phosphine oxide group was performed by a two-step Povarov-type [4+2]-cycloaddition reaction between the corresponding phosphorated aldimines with indene in the presence of BF₃·Et₂O. Subsequent oxidation of the methylene present in the structure resulted in the corresponding indeno[2,1-c]quinolin-7-one phosphine oxides 10. The synthesized derivatives were evaluated as TOP1 inhibitors showing higher inhibition values than CPT at prolonged incubation times (5 min). Inhibition of TOP1 was even observed after 30 min of incubation. The cytotoxic activities of these compounds were also studied against different cancer cell lines and a non-cancerous cell line. While some compounds showed cytotoxicity against some cancerous cells, none of the compounds showed any cytotoxicity against the non-cancerous cell line, MRC-5, in contrast to CPT, which exhibits high toxicity against this cell line. These results represent a very interesting advance since the heterocyclic phosphine oxide derivatives have important properties as TOP1 inhibitors and show an interesting cytotoxicity against different cell lines. Full article

Cyclodextrins (CDs) are natural cyclic oligosaccharides with the ability to form inclusion complexes with various organic substances. In this paper, we investigate the potential of CD complex formation to enhance the antibacterial activity and antioxidant properties of poorly soluble bioactive agents, such as chalcones, chromenes, stilbenoids and xanthylium derivatives, serving as potential adjuvants, in comparison with standard antiseptics. The interaction of these bioactive agents with the hydrophobic pocket of methyl-β-cyclodextrin (MCD) was confirmed using spectroscopic methods such as UV-vis, FTIR, ¹H and ¹³C NMR, mass-spectrometry. CD-based delivery system allows for combining multiple active agents, improving solubility, antibacterial efficacy by enhancing penetration into target bacterial cells (E. coli selectivity demonstrated via confocal microscopy). Novel compounds of chalcones and stilbenoids derivatives additionally enhance efficacy by inhibiting bacterial efflux pumps, increasing membrane permeability, and inhibiting bacterial enzymes, and showed a synergy when used in combination with metronidazole. The intricate relationship between the structural characteristics and functional properties of chalcones and stilbenoids in terms of their antibacterial and antioxidative capabilities is revealed. The substituents within aromatic rings significantly influence this activity, where position of electron-donating methoxy groups playing a crucial role. Among chalcones, stilbenoids, ana xanthyliums, the compounds caring a benzodioxol ring, analogous to natural bioactive compounds like apiol, dillapiol, and myristicin, emerge as prominent antibacterial activity. To explore the possibility to create theranostic formulations, we used fluorescent markers to visualize target cells, antiseptics to provide antibacterial activity, and bioactive agents as chalcones acting as adjuvants. Additionally, new antioxidant compounds were found such as Xanthylium derivative (R351) and chromene derivative: 1-methyl-3-(2-amino-3-cyano-7-methoxychromene-4-yl)-pyridinium methanesulfate: the pronounced antioxidant properties of these substances are observed comparable to quercetin in the efficiency. Rhodamine 6G, gentian violet, and Congo Red exhibit good antioxidant properties, although their activity is an order of magnitude lower than that of quercetin. However, they have remarkable potential due to their multifaceted nature, including the ability to visualize target cells. The most effective theranostic formulation is the combination of the antibiotic (metronidazole) + dye/fluorophore (methylene blue/rhodamine 6G) for visualization of target cells + adjuvant (chalcones or xanthylium derivatives) for antiinflammation effect. This synergistic combination, results in a promising theranostic formulation for treating bacterial infections, with enhanced efficiency, selectivity and minimizing side effects. Full article

Herein, we describe a novel coupling between ambiphilic 2-pyridylselenyl reagents and nitriles featuring an active α-methylene group. Depending on the solvent employed, this reaction can yield two distinct types of cationic pyridinium-fused selenium-containing heterocycles, 1,3-selenazolium or 1,2,4-selenadiazolium salts, in high yields. This is in contrast to what we observed before for other nitriles. Notably, the formation of selenadiazolium is reversible, gradually converting into the more thermodynamically stable selenazolium product in solution. Our findings reveal, for the first time, the reversible nature of 1,3-dipolar cyclization between the CN triple bond and 2-pyridylselenyl reagents. Nitrile substitution experiments in the adducts confirmed the dynamic nature of this cyclization, indicating potential applications in dynamic covalent chemistry. DFT calculations revealed the mechanistic pathways for new cyclizations, suggesting a concerted [3 + 2] cycloaddition for the formation of selenadiazolium rings and a stepwise mechanism involving a ketenimine intermediate for the formation of selenazolium rings. Natural bond orbital analysis confirmed the involvement of σ-hole interactions and lone pair to σ* electron donation in these processes. Additionally, theoretical investigations of σ-hole interactions were performed, focusing on the selenium-centered contacts within the new compounds. Full article

V-type nerve agents are exceedingly toxic chemical warfare agents that irreversibly inhibit acetylcholinesterase (AChE), leading to acetylcholine accumulation in synapses and the disruption of neurotransmission. VG or O.O-diethyl S-(diethylamino)ethyl phosphorothiolate was the first compound of this class that was synthesized. The selenocholines (-Se-), cholines (-O-), and methylene-cholines (-CH₂-) analogs of V-agents have been synthesized and their anti-AChE activities reported. Nevertheless, the aminocholine derivatives have not been pursued. Here, we have designed and synthesized a series of phosphorylated aminocholines analogs of VG that were characterized by NMR spectroscopy (H1, C13, P31, and TOCSY). Their pharmacological properties were analyzed in silico, while their toxicological properties were in vitro investigated using the SH-SY5Y cellular model. Despite the drug likeness of the new compounds, these fail to inhibit AChE in vitro and in cellulo. This may be partially explained by the fact that aminocholine is not a good leaving group compared to thiocholine. Remarkably, one of the compounds (P4) was found to even increase the activity of AChE. These compounds may serve as new nerve agent mimics that are safer alternatives for testing countermeasures. Importantly, P4 may act as a lead compound for developing a new class of alternative nerve agent pretreatments that are safer from pyridostigmine. Full article

A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b–79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a–79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a–79a showed no inhibition of the enzyme, in contrast to sulfamates 1b–79b. Thus, the inhibitory potential of compounds 1b–79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as K_i = 0.67 μM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme. Full article

The encapsulation of active components is currently used as common methodology for the insertion of additional functions like self-healing properties on a polymeric matrix. Among the different approaches, polyurea microcapsules are used in different applications. The design of polyurea microcapsules (MCs) containing active diisocyanate compounds, namely isophorone diisocyanate (IPDI) or hexamethylene diisocyanate (HDI), is explored in the present work. The polyurea shell of MCs is formed through the interfacial polymerization of oil-in-water emulsions between the highly active methylene diphenyl diisocyanate (MDI) and diethylenetriamine (DETA), while the cores of MCs contain, apart from IPDI or HDI, a liquid Novolac resin. The hydroxyl functionalities of the resin were either unprotected (Novolac resin), partially protected (Benzyl Novolac resin) or fully protected (Acetyl Novolac resin). It has been found that the formation of MCs is controlled by the MDI/DETA ratio, while the shape and size of MCs depends on the homogenization rate applied for emulsification. The encapsulated active compound, as determined through the titration of isocyanate (NCO) groups, was found to decrease with the hydroxyl functionality content of the Novolac resin used, indicating a reaction between NCO and the hydroxyl groups. Through the thorough investigation of the organic phase, the rapid reaction (within a few minutes) of MDI with the unprotected Novolac resin was revealed, while a gradual decrease in the NCO groups (within two months) has been observed through the evolution of the Attenuated Total Reflectance—Fourier-Transform Infrared (ATR-FTIR) spectroscopy and titration, due to the reaction of these groups with the hydroxyl functionalities of unprotected and partially protected Novolac resin. Over longer times (above two months), the reaction of the remaining NCO groups with humidity was evidenced, especially when the fully protected Acetyl Novolac resin was used. HDI was found to be more susceptible to reactions, as compared with IPDI. Full article

This review covers the last 25 years of the literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as vorinostat) acting as an HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds displayed good to excellent inhibitory activity against HDACs and in many cases showed antiproliferative activity against human cancer cell lines. Full article

Novel hybrid TiO₂-based materials were obtained by adsorption of two different porphyrins on the surface of nanoparticles—commercially available 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and properly modified metalloporphyrin—5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin palladium(II) (PdF₂POH). The immobilization of porphyrins on the surface of TiO₂ was possible due to the presence of sulfonyl groups. To further elevate the adsorption of porphyrin, an anchoring linker—4-hydroxybenzoic acid (PHBA)—was used. The synthesis of hybrid materials was proven by electronic absorption spectroscopy, dynamic light scattering (DLS), and photoelectrochemistry. Results prove the successful photosensitization of TiO₂ to visible light by both porphyrins. However, the presence of the palladium ion in the modifier structure played a key role in strong adsorption, enhanced charge separation, and thus effective photosensitization. The incorporation of halogenated metalloporphyrins into TiO₂ facilitates the enhancement of the comprehensive characteristics of the investigated materials and enables the evaluation of their performance under visible light. The effectiveness of reactive oxygen species (ROS) generation was also determined. Porphyrin-based materials with the addition of PHBA seemed to generate ROS more effectively than other composites. Interestingly, modifications influenced the generation of singlet oxygen for TPPS but not hydroxyl radical, in contrast to PdF₂POH, where singlet oxygen generation was not influenced but hydroxyl radical generation was increased. Palladium (II) porphyrin-modified materials were characterized by higher photostability than TPPS-based nanostructures, as TPPS@PHBA-P25 materials showed the highest singlet oxygen generation and may be oxidized during light exposure. Photocatalytic activity tests with two model pollutants—methylene blue (MB) and the opioid drug tramadol (TRML)—confirmed the light dose-dependent degradation of those two compounds, especially PdF₂POH@P25, which led to the virtually complete degradation of MB. Full article

Active methylene compounds such as thioamides are widely used in the organic chemistry for the construction of a variety of heterocyclic systems, such as thieno[2,3-b]pyridines, 1,2,4-dithiazoles, isothiazoles, 1,2,3-thiadiazoles, etc. N,N′-Diphenyldithiomalondiamide (dithiomalondianilide) as a compound with methylene active group is also of interest as a starting reagent for the synthesis of new N,S-containing heterocycles with potential pharmacological application. However, the reactions of dithiomalondianilide are poorly studied. In the present study, we report the synthesis of new 4,5,6,7-tetrahydro[1,2]dithiolo[3,4-b]dithiolopyridine-5-carboxamides through the reaction of dithiomalondianilide with 3-aryl-2-cyanoacrylamides. The products were characterized using FTIR and NMR spectroscopy as well as X-ray analysis. Full article

As mitochondria are negatively charged organelles, penetrating cations are used as parts of chimeric molecules to deliver specific compounds into mitochondria. In other words, they are used as electrophilic carriers for such chemical moieties as antioxidants, dyes, etc., to transfer them inside mitochondria. However, unmodified penetrating cations affect different aspects of cellular physiology as well. In this review, we have attempted to summarise the data about the side effects of commonly used natural (e.g., berberine) and artificial (e.g., tetraphenylphosphonium, rhodamine, methylene blue) penetrating cations on cellular physiology. For instance, it was shown that such types of molecules can (1) facilitate proton transport across membranes; (2) react with redox groups of the respiratory chain; (3) induce DNA damage; (4) interfere with pleiotropic drug resistance; (5) disturb membrane integrity; and (6) inhibit enzymes. Also, the products of the biodegradation of penetrating cations can be toxic. As penetrating cations accumulate in mitochondria, their toxicity is mostly due to mitochondrial damage. Mitochondria from certain types of cancer cells appear to be especially sensitive to penetrating cations. Here, we discuss the molecular mechanisms of the toxic effects and the anti-cancer activity of penetrating cations. Full article