Search Results (161)

A triphenylphosphine-functionalized silica gel material, optimized for lead adsorption, was synthesized via a one-pot sol–gel reaction and characterized using FTIR and solid-state ¹³C and ²⁹Si NMR and XPS spectroscopy. The interaction between lead cations and phosphine groups was evaluated using the ³¹P NMR chemical shift tensor as a sensor. Two distinct types of phosphine groups, exhibiting different rotational mobility behaviors, were identified, with their ratio influenced by the presence of lead cations. These results suggest that the adsorption behavior of lead on this functionalized silica gel adsorbent can be directly evaluated by its lead–phosphorus interaction. This association was corroborated by the shifting of the binding energies of phosphorus functional groups after lead uptake in the XPS analysis. Full article

Background/Objectives: Cancer remains a major global health challenge, driving the search for novel chemotherapeutic agents. This study aimed to evaluate the structural and biological properties of a series of Pd(II) complexes containing triphenylphosphine and thiosemicarbazone ligands, in order to assess their potential as anticancer agents. Methods: Six Pd(II) complexes with the general formula [PdCl(PPh₃)(TSC)] were synthesized and fully characterized by NMR (¹H, ¹³C, ³¹P), FTIR, mass spectrometry, and X-ray diffraction. Their cytotoxic effects were investigated through in vitro assays using 2D and 3D cancer cell models, including clonogenic, wound healing, cell cycle, and apoptosis assays via flow cytometry. Results: Complexes from the B family demonstrated significantly higher cytotoxicity than those from the C family, particularly against ovarian (IC₅₀ < 1 µM) and breast (IC₅₀~2 µM) cancer cell lines. These compounds exhibited superior potency and selectivity compared to cisplatin, with high selectivity indices toward non-tumor cells. Mechanistic studies revealed both cytotoxic and cytostatic effects depending on structural variations, with apoptosis identified as the primary mechanism of cell death. PdB1, in particular, induced a marked increase in late apoptotic populations and maintained its cytotoxic activity in 3D spheroid models by promoting disintegration, loss of cell adhesion, and nuclear fragmentation. Conclusions: The findings underscore the therapeutic promise of Pd(II) complexes, especially PdB1, as potent and selective antineoplastic agents capable of acting effectively in complex tumor environments and potentially overcoming chemoresistance. Full article

Formononetin is widely used in anti-tumor research, but its poor water solubility leads to low absorption and poor utilization efficiency in vivo, limiting further development. The triphenylphosphine cation was partially attached to the 7-position hydroxyl group of formononetin to specifically target it into the mitochondria of tumor cells to enhance the anti-tumor effect. Detailed structural characterization via ¹H-NMR and ¹³C-NMR analysis confirmed the physical properties and chemical structures of 21 newly synthesized derivatives. The effects of these derivatives on tumor cells were assessed by in vitro and computational methods. MTT results from four tumor cell lines showed that formononetin derivatives containing triphenylphosphine had stronger anti-tumor activity than formononetin and exhibited more cytotoxic effects in cancer cells than in normal cells. In particular, the final product 2c (IC₅₀ = 12.19 ± 1.52 μM) showed more potent anti-tumor activity against A549 cells. It was also superior to formononetin and 5-FU. To identify the potential biological targets, the core-expressed gene SHMT2 in lung cancer mitochondria was screened using network pharmacology technology, and molecular docking analysis confirmed the stable binding of the end products to the amino acid residues of the core genes through the formation of hydrogen bonds and via other interactions. In addition, molecular docking simulations further confirmed that the end product exhibited excellent stability when bound to SHMT2. These results suggest that triphenylphosphine-containing formononetin derivatives are worthy of further exploration in the search for novel drug candidates for the treatment of cancer. Full article

Background/Objectives: Latanoprost is a leading active pharmaceutical ingredient belonging to the synthetic prostaglandin F2α analogs, widely used as a first-line treatment for open-angle glaucoma and increased intraocular pressure. This study addresses the critical need for an accurate and precise chromatographic method that is capable of simultaneously quantifying latanoprost and six latanoprost-related substances in antiglaucoma eye drops. This will be crucial for patient safety and treatment efficacy. This method enables the separation of latanoprost isomers, (15S)-latanoprost, latanoprost enantiomer, and 5,6-trans latanoprost from latanoprost signal. Furthermore, it is specific for the well-known latanoprost degradants—the major latanoprost acid and the minor 15-ketolatanoprost—as well as synthetic derivatives, such as triphenylphosphine oxide (TPPO) and propan-2-yl 5-(diphenylphosphoryl)pentanoate (IDPP). Using forced degradation studies using high temperatures, UV light, alkalis, acids, and oxidizing agents, the degradation profiles of the drugs were characterized and the method’s stability-indicating power was confirmed. Methods: Separation was achieved on a stationary combined system comprising chiral and cyano columns. Reverse-phase gradient elution and UV 210 nm detection were employed. The novel method was validated according to the European Medicines Agency International Council for Harmonisation Q2 Validation of analytical procedures—Scientific guideline. Results: The method was shown to be linear in the range of 40–60 µg/mL for latanoprost and 0.05–2.77 µg/mL for related substances, confirmed by a correlation coefficient of r = 0.999. Recoveries for latanoprost were obtained within the range of 98.0–102.0% for assays and 90.0–110.0% for impurities. The detection and quantification limits for latanoprost were 0.025 µg/mL and 0.35 µg/mL, respectively. Conclusions: The analytical procedure developed is adequately sensitive, precise, and accurate compared to existing methods. The method can be reliably used to control the critical quality attributes of low-dose latanoprost products, ensuring their required high pharmaceutical quality, which translates into improvements in patient care. This advancement holds significant implications for enhancing the therapeutic management of glaucoma, ensuring drug safety and efficacy. Full article

Anxiety and stress-related disorders affect all ages in all geographical areas. As high anxiety and chronic stress result in the modulation of mitochondrial pathways, intensive research is being carried out on pharmaceutical interventions that alleviate pertinent symptomatology. Therefore, innovative approaches being currently pursued include substances that target mitochondria bearing an antioxidant moiety. In this study, a newly synthesized antioxidant consisting of triphenylphosphine (TPP), a six-carbon alkyl spacer, and hydroxytyrosol (HT) was administered orally to mice via drinking water. Cerebellum and liver samples were collected and analyzed using ultra-high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) to assess the levels of TPP-HT in the respective tissues to evaluate in vivo administration efficacy. Sample preparation included extraction with appropriate solvents and a preconcentration step to achieve the required sensitivity. Both methods were validated in terms of selectivity, linearity, accuracy, and limits of detection and quantification. Additionally, a workflow for evaluating and statistically summarizing multiple fortified calibration curves was devised. TPP-HT penetrates the blood–brain barrier (BBB), with a level of 11.5 ng g⁻¹ quantified in the cerebellum, whereas a level of 4.8 ng g⁻¹ was detected in the liver, highlighting the plausibility of orally administering TPP-HT to achieve mitochondrial targeting. Full article

Two phenoxy-ketimines ligands, 2-(1-(benzylimino)ethyl)phenol (HL^BSMe) and 2-((benzylimino)(phenyl)methyl)phenol (HL^BSPh), were synthesized and used as supporting ligands of new copper(II), copper(I), and silver(I) complexes. In order to confer different solubility properties to the metal complexes and to stabilize Cu and Ag in their +1 oxidation state, the lipophilic triphenylphosphine (PPh₃) and the hydrophilic 1,3,5-triaza-7-phosphaadamantane (PTA) were selected as co-ligands in the syntheses of the Cu(I) and Ag(I) complexes. All compounds were characterized by CHN analysis, NMR, FT-IR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS); the molecular structure of the copper(II) complex [Cu(L^BSPh)₂] was also determined by single-crystal X-ray diffraction. Finally, the antibacterial activity of the metal complexes, the Schiff base ligands and phosphane co-ligands, were assessed by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Full article

The Vinca alkaloid vindoline was coupled at position 17 with several trisubstituted phosphine derivatives and their in vitro anticancer activities on 60 human tumor cell lines (NCI60) were investigated. This phosphonium-type ionic side chain is beneficial because it allows therapeutic molecules to pass through the cell membrane. Thus, the candidates coupled to it can exert their activities in the mitochondria. The coupling of vindoline with the trisubstituted phosphines was achieved through flexible or rigid linkers. Instead of the ionic phosphonium structural part, a neutral moiety, namely the triphenylmethyl group, was also added to the side chain, being sterically similar but without a charge and phosphorus atom. In addition, the triphenylphosphine element was also built at position 10 of vindoline. Most of the derivatives showed low micromolar growth inhibition (GI₅₀) values against most cell lines. Among them, conjugate 9e was outstanding: it exhibited nanomolar anticancer activity on the RPMI-8226 leukemia cell line (GI₅₀ = 20.0 nM). Compound 9g elicited cell cycle disturbance and apoptosis on A2780 ovary cancer cells and inhibited their migration at subantiproliferative concentrations. The selectivity of the conjugates was determined by their effects on non-tumor Chinese hamster ovary (CHO) cells in the CellTiter-Glo Luminescent Cell Viability Assay. Compound 9e showed an estimated half-maximal inhibitory concentration (IC₅₀) value of 1.36 µM, suggesting good selectivity on cancer cells. These results open new perspectives of novel phosphonium-based vindoline derivatives as anticancer compounds. Full article

Tumorigenesis and progression are closely associated with apoptosis and primarily regulated by mitochondria, which are considered major targets for cancer therapy. In this study, twelve novel icaritin (ICT) derivatives were designed and synthesized, four of which were specifically targeted to mitochondria. Biological studies demonstrated that all compounds containing triphenylphosphine (TPP⁺) exhibited a substantial increase in antitumor activity compared to ICT and control compounds while also exhibiting notable selectivity for tumor cells over normal cells. Among these derivatives, Mito-ICT-4 exhibited the strongest antiproliferative effect, with an IC₅₀ value of 0.73 ± 0.06 μM for BEL-7402 cells, which is 29 times lower than that of ICT, and an IC₅₀ value of 67.11 ± 2.09 μM for HEK293 cells, indicating approximately 33-fold selectivity for tumor cells. High-performance liquid chromatography (HPLC) analysis revealed that Mito-ICT-4 significantly accumulated in the mitochondria of BEL-7402 cells, with the level of accumulation approximately 2.5 times greater than that of ICT. Further investigations demonstrated that upon entering the mitochondria of tumor cells, Mito-ICT-4 downregulated SIRT3 protein expression, disrupted intracellular redox homeostasis, and led to a substantial increase in mitochondrial ROS levels, abnormal CypD-dependent MPTP opening, mitochondrial membrane potential depolarization, and ROS release into the cytoplasm, ultimately triggering ROS-mediated apoptosis in BEL-7402 cells. Transcriptomic analysis identified differentially expressed genes and enriched pathways, highlighting the ROS-mediated p38-MAPK signaling pathway as a key mediator of Mito-ICT-4-induced mitochondria-dependent apoptosis. The effects of Mito-ICT-4 on the expression of key genes (SIRT3, CypD, P-MKK6, P-P38, and DDIT3) were further validated by qRT-PCR and Western blot analysis, with results aligning with transcriptomic data. The novel ICT derivatives synthesized in this study, with mitochondria-targeting functionality, provide a basis for the development of targeted antitumor drugs. Full article

Herein, nine square planar trans-arylbis(triphenylphosphine)palladium halides (PdX(PPh₃)₂Ar) were synthesized and fully characterized. The molecular structure of two complexes (1 and 2) have been determined by both X-ray diffraction and described thanks to Hirshfeld surface analysis. Investigation of the antioxidant activities showed that most of the complexes exhibit a strong dose-dependent radical scavenging activity towards DPPH radical as well as in the ABTS radical scavenging test. Complexes 1 [PdI(PPh₃)₂(4-MeOC₆H₄)] and 3 [PdCl(PPh₃)₂(4-MeOC₆H₄)] showed the highest activity in the DPPH assay with EC₅₀ values of 1.14 ± 0.90 and 1.9 ± 0.87 µM, respectively. In contrast, for the ABTS assay, quercetin (5.56 ± 0.97 µM) was slightly more efficient than the three complexes 1 (5.78 ± 0.98 µM), 2 (7.01 ± 0.98 µM), and 3 (11.12 ± 0.94 µM). The use of kinetic studies as a powerful parameter shows that complexes 1, 2, and 3 displayed the best antioxidant efficiency. The antioxidant effect of the nine palladium complexes has been also evaluated on the enzyme-catalyzed oxidation of the L012 probe (using HRP/H₂O₂) by using a chemiluminescence technique. As with the last model, complexes 1, 2, and 3 showed the best activity, with EC50 values of 3.56 ± 1.87, 148 0.71, and 5.8 ± 2.60 µM, respectively. Interestingly, those complexes (1, 2, and 3) even exhibited a higher dose-dependent activity than the quercetin (7.06 ± 2.56 µM) used as a standard. Taken together, the combined results reveal that the antiradical and enzyme (HRP) inhibitory activity of complexes decrease following the ligand order of p-OMePh > p-OAcPh >> Ph. Full article

A spherical amide with C₃ symmetry was synthesized by a one-step cyclization reaction using triphenylphosphine and hexachloroethane as coupling reagents. This method enabled synthesis of N-benzyl and N-allyl derivatives, which could not be obtained by the previously reported method. The optical resolution of each compound was measured, and their electronic circular dichroism spectra revealed that they were mirror images. The high structural symmetry resulted in a higher Δε (molar absorption difference against right or left circular polarization: ε_L − ε_R value compared to that of another structural isomer synthesized previously. The absolute structure of the enantiopure crystal of the N-benzyl derivative was determined using the Flack parameter obtained by X-ray crystallographic analysis. Full article

Background/Objectives: Breast cancer (BC) remains one of the most prevalent and deadly cancers worldwide, with limited access to advanced treatments in developing regions. There is a critical need for novel therapies with unique mechanisms of action, especially to overcome resistance to conventional platinum-based drugs. This study investigates the anticancer potential of the ruthenium complex Bis(quinolin-8-olato)bis(triphenylphosphine)ruthenium(II) (Ru(quin)₂) in ER-positive (T47D) and triple-negative (MDA-MB-231) BC cell lines. Results: Ru(quin)₂ demonstrated dose-dependent cytotoxicity, with IC50 values of 48.3 μM in T47D cells and 45.5 μM in MDA-MB-231 cells. Its cytotoxic effects are primarily driven by apoptosis, as shown by increased BAX expression, enhanced caspase-3 activity, reduced Aurora B kinase levels, and elevated histone release. Ru(quin)₂ also induced autophagy, evidenced by LC3-I to LC3-II conversion and reduced SQSTM1, partially mediated through MAPK signaling. Furthermore, Ru(quin)₂ induced G0/G1 cell cycle arrest by downregulating cyclin D1, CDK4, and CDK6, alongside upregulation of the CDK inhibitor p21. Conclusions: Ru(quin)₂ emerges as a potent candidate for BC treatment, with multiple mechanisms of action involving apoptosis, autophagy, and cell cycle arrest. Further studies are warranted to elucidate its detailed molecular mechanisms and evaluate its therapeutic potential in vivo, moving toward clinical applications for both ER-positive and triple-negative BC management. Full article

Three 1,1-diethoxyalk-3-yn-2-ones underwent isomerization and gave only the corresponding (3E,5E)-alkadienones in 72–87% yield when subjected to polystyrene-supported triphenylphosphine at 60 °C using acetylacetone as a co-catalyst. As a first step to make the dienes electron richer, the diethoxyacetyl moiety was reduced with sodium borohydride under Luche conditions and afforded the corresponding alcohols, with a 92% yield in the best case. Full article

Heteroleptic coumarin-based silver(I) complexes with improved solubility profiles were synthesised using either triphenylphosphine or an N-heterocyclic carbene as adduct ligands, and were fully characterised using IR and NMR spectroscopy, elemental analysis, and, where possible, X-ray crystallography. The triphenylphosphine adducts formed well-resolved structures, where the oxyacetate ligands asymmetrically chelated the silver(I) ion in a bidentate chelating mode, and the silver(I) ion was also bound to two triphenylphosphine ligands. The solubility profile and photostability of the adducts were considerably improved compared to those of previously isolated simple coumarin silver(I) complexes. Analysis of the coumarin N-heterocyclic carbene(NHC) silver(I) adduct indicated that it likely formed as a complex aggregate species with an overall stoichiometry of 1:1:1 coumarin:Ag(I):NHC. The Kirby Bauer assay and broth microdilution assays were used to assess the silver(I) complexes’ and adducts’ antimicrobial activity against pathogenic strains of Pseudomonas aeruginosa, Escherichia coli, and MRSA. Interestingly, the formation of more soluble complexes did not increase the activity of the silver(I) complexes and, in effect, made them less effective antimicrobial agents, particularly against Escherichia coli and Pseudomonas aeruginosa, although they retained their activity against MRSA. Full article

(Triphenylphosphoranylidene)succinic anhydride, which is prepared from triphenylphosphine and maleic anhydride and is itself not reactive towards aryl aldehydes, is ring-opened with methanol to methyl (triphenylphosphoranylidene)succinate. In one pot, the newly formed phosphorane is reacted with aryl aldehydes to methyl aryl itaconates, which are subsequently hydrolyzed with aqueous sodium hydroxide to aryl itaconic acids. The biological activity of 12 aryl itaconic acids thus prepared against four gram-positive and four gram-negative bacterial strains has been studied. Full article

Within this study, we report a simple two-step process for the synthesis of perfluoroalkylated pyrazoles from aliphatic aldehydes. In the photocatalytic first step, the aldehydes are transformed into the corresponding perfluoroalkylated enals, which then undergo nucleophilic attack by hydrazine and subsequent ring closure, providing the fluorinated 3,4-substituted pyrazole products in a 64–84% yield. Using triphenylphosphine and imidazolidinone as organocatalysts, the method is operationally simple and omits heavy metal-containing waste. Full article