Search

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds. [ABSTRACT FROM AUTHOR]

Stimulus-responsive materials hold significant promise for antitumor applications due to their variable structures and physical properties. In this paper, a series of peptides with a responsive viologen derivative, Pep-CnV (n = 1, 2, 3) were designed and synthesized. The process and mechanism of the interaction were studied and discussed. An ultraviolet–visible (UV) spectrophotometer and fluorescence spectrophotometer were used to study their redox responsiveness. Additionally, their secondary structures were measured by Circular Dichroism (CD) in the presence or absence of the reductant, Na2SO3. DPPC and DPPG liposomes were prepared to mimic normal and tumor cell membranes. The interaction between Pep-CnV and biomembranes was investigated by the measurements of surface tension and cargo leakage. Results proved Pep-CnV was more likely to interact with the DPPG liposome and destroy its biomembrane under the stimulus of the reductant. And the destruction increased with the length of the hydrophobic tail chain. Pep-CnV showed its potential as an intelligent antitumor agent. [ABSTRACT FROM AUTHOR]

Reactions of a chromone‐based hydrazone (SalHFC; HL) with Ni(II), Co(II), and Cd(II) ions yielded new solid chelates with the general formula [M(L)X].nZ, M = Ni(II), Co(II) and Cd(II), X = NO3− or OAc−, n = 0.5–2, Z = H2O or EtOH for complexes 1, 3, 4, 6, 7, 8 and [M2(L)(OAc)3X].0.5EtOH.nH2O, M = Ni(II) and Co(II), X = H2O or EtOH, n = 1 or zero for complexes 2 and 5. The synthesized chelates have been successfully characterized by means of different analytical and spectroscopic tools. SalHFC performs as a monoanionic tridentate in all chelates except chelate 2 and 5 (monoanionic tetradentate). Molar conductivity measurements demonstrated a non‐electrolytic manner of all chelates. Nickel(II) and cobalt(II)‐SalHFC chelates displayed tetrahedral geometries whereas cadmium(II) chelates (7 and 8) were octahedral. TG was employed to inspect the thermal degradation patterns of SalHFC‐complexes, and the Coats‐Redfern equations were employed to estimate the kinetic parameters of the thermal degradation steps. Density functional theory (DFT) level implementation in the Gaussian 09 program at B3LYP/6‐311G(d,p) level was efficaciously used to predict the molecular structural properties of SalHFC and its chelates and the theoretical data and experimental findings were then integrated. SalHFC and its chelates displayed anticancer action against the HepG2 cell line and the results were verified by molecular docking studies. [ABSTRACT FROM AUTHOR]

Background: Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, and prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with homologous recombination deficiency (HRD), PARP1 selective inhibitors such as saruparib (AZD5305) are being developed. It is expected that selective PARP1 inhibition leads to a safer profile that facilitates its combination with other DNA damage repair inhibitors. Here, we aimed to characterize the antitumor activity of AZD5305 in patient-derived preclinical models compared to the first-generation PARP1/2 inhibitor olaparib and to identify mechanisms of resistance. Methods: Thirteen previously characterized patient-derived tumor xenograft (PDX) models from breast, ovarian, and pancreatic cancer patients harboring germline pathogenic alterations in BRCA1, BRCA2, or PALB2 were used to evaluate the efficacy of AZD5305 alone or in combination with carboplatin or an ataxia telangiectasia and Rad3 related (ATR) inhibitor (ceralasertib) and compared it to the first-generation PARPi olaparib. We performed DNA and RNA sequencing as well as protein-based assays to identify mechanisms of acquired resistance to either PARPi. Results: AZD5305 showed superior antitumor activity than the first-generation PARPi in terms of preclinical complete response rate (75% vs. 37%). The median preclinical progression-free survival was significantly longer in the AZD5305-treated group compared to the olaparib-treated group (> 386 days vs. 90 days). Mechanistically, AZD5305 induced more replication stress and genomic instability than the PARP1/2 inhibitor olaparib in PARPi-sensitive tumors. All tumors at progression with either PARPi (39/39) showed increase of HRR functionality by RAD51 foci formation. The most prevalent resistance mechanisms identified were the acquisition of reversion mutations in BRCA1/BRCA2 and the accumulation of hypomorphic BRCA1. AZD5305 did not sensitize PDXs with acquired resistance to olaparib but elicited profound and durable responses when combined with carboplatin or ceralasertib in 3/6 and 5/5 models, respectively. Conclusions: Collectively, these results show that the novel PARP1 selective inhibitor AZD5305 yields a potent antitumor response in PDX models with HRD and delays PARPi resistance alone or in combination with carboplatin or ceralasertib, which supports its use in the clinic as a new therapeutic option. [ABSTRACT FROM AUTHOR]

The Japanese plum tree (Prunus salicina Lindl.) is mainly cultivated in temperate areas of China and some European countries. Certain amounts of wood (from pruning works) are generated every year from this crop of worldwide commercial significance. The main objective of this work was to value this agricultural woody residue, for which the chemical composition of pruning wood extracts from six Japanese plum cultivars was investigated, and the antiproliferative activity of extracts and pure phenolics present in those extracts was measured. For the chemical characterization, total phenolic content and DPPH radical-scavenging assays and HPLC‒DAD/ESI‒MS analyses were performed, with the procyanidin (−)-ent-epicatechin-(2α→O→7,4α→8)-epicatechin (5) and the propelargonidin (+)-epiafzelechin-(2β→O→7,4β→8)-epicatechin (7) being the major components of the wood extracts. Some quantitative differences were found among plum cultivars, and the content of proanthocyanidins ranged from 1.50 (cv. 'Fortune') to 4.44 (cv. 'Showtime') mg/g of dry wood. Regarding the antitumoral activity, eight wood extracts and four phenolic compounds were evaluated in MCF-7 cells after 48 h of induction, showing the wood extract from cv. 'Songold' and (‒)-annphenone (3), the best antiproliferative activity (IC50: 424 μg/mL and 405 μg/mL, respectively). [ABSTRACT FROM AUTHOR]

Silybin is a natural flavonolignan with potential anticancer, antioxidant, and hepatoprotective properties. In the present study, various loadings of silybin (1, 3, and 5 wt%) were encapsulated in poly-ε-caprolactone (PCL) fibers by electrospinning, in order to produce new pharmaceutical composites with improved bioactive and drug delivery properties. The morphological characteristics of the composite fibrous structures were evaluated by scanning electron microscopy (SEM), and the encapsulation efficiency and the release rate of silybin were quantified using a UV-Vis spectrophotometer. The analysis of the membranes' thermal behavior by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) revealed the existence of interaction between PCL and silybin. An investigation of the cytocompatibility of the composite membranes revealed that normal cells displayed an unimpeded proliferation in the respective silybin concentrations; however, tumor cell growth demonstrated a dose-dependent inhibition. Furthermore, an effective antioxidant activity against hydrogen peroxide-induced oxidative stress in HEK-293 cells was observed for the prepared electrospun fibrous mats. [ABSTRACT FROM AUTHOR]

A new novel tetradentate ligand, [(1E,1′E)‐N,N′‐(1,2‐phenylene)bis(1‐(5‐(2‐fluorophenyl)furan‐2‐yl)methanimine) (PFPFMI), and its nano‐sized [Zn(PFPFMI)Cl2].3H2O complex were synthesized. The geometry of PFPFMI and its Zn(II) complex was described through CHN analyses, Fourier‐transform infrared spectroscopy (FTIR), UV–visible, X‐ray diffraction (XRD), thermal gravimetric analysis (TGA), and mass spectral data tests. The spectral data of the nano‐sized [Zn(PFPFMI)Cl2].3H2O complex indicates that the PFPFMI ligand functions as a tetradentate (N2O2) coordination through two azomethine nitrogen groups (N) and two furan ring oxygen (O) atoms. Density functional theory (DFT) calculations were performed using the molecular studio software to investigate the optimal geometry of PFPFMI and its [Zn(PFPFMI)Cl2].3H2O complex. The SEM, TEM, XRD, AFM, and energy dispersive X‐ray analysis (EDX) analyses of the studied complex unveil distinct and strong diffraction peaks, indicating its crystalline nature and providing evidence of its nano‐sized particle sizes. Additionally, the inhibition zone diameter was used to assess the in vitro antimicrobial action of PFPFMI and the particular complex against Gram‐positive bacteria Streptococcus pneumonia and Bacillus subtilis, Gram‐negative bacteria Pseudomonas aeruginosa, Salmonella typhi, and Escherichia coli, as well as fungi Aspergillus fumigatus, Geotricum candidum, Syncephalastrum racemosum, and Candida tropicalis. The [Zn(PFPFMI)Cl2].3H2O complex exhibits higher activity than the ligand PFPFMI. In vitro cytotoxicity of the synthesized [Zn(PFPFMI)Cl2].3H2O complex was explored using MCF7 (breast cancer), HCT116 (colon cancer), A549 (lung cancer), HePG‐2 (liver cancer), A375 (melanoma cancer), and normal lung fibroblast (WI38) cell lines. Based on IC50 and selective index (SI) values, it was shown that the complex exhibited higher potency against MCF7 cell lines. Moreover, the Zn(II) complex exhibited the ability to induce DNA damage in MCF7 cells, resulting in dose‐dependent cell apoptosis. Subsequent investigations revealed that complex 2 also induced cell cycle arrest in the G2 and S phases. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), one of the malignancies with a wide expression of stress ligands recognized by Vδ1γδ T cells, has received much attention in adoptive immunotherapy of γδ T cells. In this study, we aimed to identify the potential anti-tumor Vδ1γδ T subpopulations in HCC. Healthy donors (HDs) and HCC patients were recruited from the Affiliated Cancer Hospital of Zhengzhou University. Blood and tumor tissue samples were obtained respectively. Bioinformatics methods were used to analyze total γδ T cells and subsets infiltration, overall survival of HCC patients with high and low infiltration level of Vδ1γδ T cells, and IFNG , granzyme A, granzyme B and perforin expression in TRDV1 high/low CD69 high/low groups. CD69 expression and Vδ1γδT cells infiltration in HCC were detected by immunofluorescence. Phenotypic analysis of Vδ1γδ T cells in blood and tumor tissue samples were performed by flow cytometry. Vδ1γδ T cells infiltrating in HCC were associated with better clinical outcome. Study in tumor micro-environment (TME) of HCC demonstrated that not total Vδ1γδ T but CD69+ Vδ1γδ subset infiltration was associated with smaller tumor volume. Moreover, HCC patients simultaneously with high TRDV1 and CD69 expression produced more effector molecules and had longer survival time. Since Vδ1γδ T cells in the tumor microenvironment were often difficult to access, we demonstrated that CD69+ Vδ1γδ T cells also existed in peripheral blood mononuclear cells (PBMC) of HCC and displayed enhanced cytotoxic potentials than HDs. Finally, we investigated the functions and found that CD69+ Vδ1γδ T cells exhibited stronger tumor reactivities when challenged by tumor cells. CD69+ Vδ1γδ T cells are functional Vδ1γδ T cell subsets in patients with HCC. Circulating CD69+ Vδ1γδ T cell is a promising candidate in immunotherapy of HCC. [Display omitted] • Vδ1γδ T associated with better clinical outcome of HCC. Higher CD69+ Vδ1γδ subset indicated smaller tumor. • CD69+ Vδ1γδ Tfrom PBMCs displayed enhanced cytotoxicity. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and poses a severe threat to human health. Ginkgo biloba leaf polysaccharide (GBLP) is a bioactive component, and its sulphated derivative (sulfated GBLP, SGBLP) may exhibit high antitumor activity in certain types of cancers. However, the precise mechanisms of the SGBLP antitumor activity, particularly in HCC, remain unclear. Here, we assessed the effect of SGBLP on HepG2 hepatocellular carcinoma cells. SGBLP was shown to inhibit cellular proliferation and promote apoptosis through the regulation of pro- as well as anti-apoptosis markers, and to induce autophagy by supressing the PI3K/AKT/mTOR pathway. In addition, the autophagy inhibitor 3-melyladenine (3-MA) enhanced the antiproliferative and proapoptotic effects of SGBLP in HepG2 cells. Thus, SGBLP exhibits antitumor activity, and its combination with an autophagy inhibitor may represent a promising anticancer strategy in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Sporisorium reilianum is an important biotrophic pathogen that causes head smut disease. Polysaccharides extracted from diseased sorghum heads by Sporisorium reilianum exhibit significant medicinal and edible value. However, the structure and biological activities of these novel polysaccharides have not been explored. In this study, a novel polysaccharide (WM-NP'-60) was isolated and purified from the fruit bodies of S. reilianum and aimed to explore the structural characteristics and substantial antioxidant and antitumor properties of WM-NP'-60. Monosaccharide composition determination, periodate oxidation-Smith degradation, 1D/2D-NMR analysis, and methylation analysis revealed that WM-NP'-60 consisted mainly of β-1,6-D-Glcp, β-1,3-D-Glcp, and β-1,3,6-D-Glcp linkages. The antioxidant assays demonstrated that WM-NP'-60 exhibited great activities, including scavenging free radicals, chelating ferrous ions, and eliminating reactive oxygen species (ROS) within cells. The HepG2, SGC7901, and HCT116 cells examined by transmission electron microscopy (TEM) revealed typical apoptotic bodies. Therefore, a novel fungal polysaccharide (WM-NP'-60) was discovered, extracted, and purified in this experiment, with the aim of providing a reference for the development of a new generation of food and nutraceutical products suitable for human consumption. [ABSTRACT FROM AUTHOR]

In the present research, we have successfully synthesized and characterized two novel Bis-chalcones, namely 3-(4-(dimethylamino)benzylidene)pentane-2,4-dione (DBPD) and 3-(3-(4-dimethylamino)phenyl)allylidene)pentane-2,4-dione (DPAPD). Their photophysical properties were studied in a series of solvents. UV–Vis absorption spectra are insensitive to solvent polarity whereas the fluorescence spectra in the same solvent set show an important solvatochromic effect leading to large Stokes shifts. Linear solvation energy relations were employed to correlate the position of fluorescence spectra maxima with microscopic empirical solvent parameters. This study indicates that important intramolecular charge transfer, ICT, takes place during the excitation process. Furthermore, we extended our investigations to encompass absorption and fluorescence behaviors in mixed water-EtOH environments, allowing us to gauge microenvironmental polarity. DFT method with B3LYP/6-311++G(d,p) basis set has been used to analyze DBPD and DPAPD computationally, and to determine the most stable structure and the nature of the molecular orbitals, which are essential to understand the binding feature of the compounds. The experimental data from NMR, UV–Vis and FTIR were compared with the theoretical calculations of electronic and conformational properties. Moreover, the QTAIM (RDG) topological analysis was applied to both compounds using Multiwfn software. Also, we delved into the determination of binding constants and the assessment of micellar properties, including polarity and critical micelle concentration. The dynamic interactions between the investigated dyes and CT-DNA were investigated using electronic absorption and emission techniques. In the closing phases of our research, we delved into the exploration of the potential antitumor activity exhibited by the synthesized compounds. Moreover, the docking binding affinity of investigated compounds toward CT-DNA and tumors protein were estimated by the Schrödinger suite software. [ABSTRACT FROM AUTHOR]

CD39 serves as a crucial biomarker for neoantigen-specific CD8+ T cells and is associated with antitumor activity and exhaustion. However, the relationship between CD39 expression levels and the function of chimeric antigen receptor T (CAR-T) cells remains controversial. This study aimed to investigate the role of CD39 in the functional performance of CAR-T cells against hepatocellular carcinoma (HCC) and explore the therapeutic potential of CD39 modulators, such as mitochondrial division inhibitor-1 (mdivi-1), or knockdown CD39 through short hairpin RNA. Our findings demonstrated that glypican-3-CAR-T cells with moderate CD39 expression exhibited a strong antitumor activity, while high and low levels of CD39 led to an impaired cellular function. Methods modulating the proportion of CD39 intermediate (CD39int)-phenotype CAR-T cells such as mdivi-1 and CD39 knockdown enhanced and impaired T cell function, respectively. The combination of mdivi-1 and CD39 knockdown in CAR-T cells yielded the highest proportion of infiltrated CD39int CAR-T cells and demonstrated a robust antitumor activity in vivo. In conclusion, this study revealed the crucial role of CD39 in CAR-T cell function, demonstrated the potential therapeutic efficacy of combining mdivi-1 with CD39 knockdown in HCC, and provided a novel treatment strategy for HCC patients in the field of cellular immunotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULT CONCLUSION Xanthohumol is an isopentadienyl flavonoid in hops, which have several pharmacological effects. However, due to the poor bioavailability of xanthohumol, it cannot be widely used.In this study, solvent extraction combined with preparative liquid chromatography was used to separate and purify xanthohumol in hop residue. And the purity, yield and recovery of xanthohumol was 983.0 ± 2.1 g kg−1, 921.61 ± 5.65 g kg−1, and 5.41 ± 0.07 g kg−1, respectively. Response surface methodology optimization revealed that 216.75 g kg−1 ethyl oleate, 574.1 g kg−1 polyoxyl‐35 castor oil (EL35) and 209.15 g kg−1 polyethylene glycol 200 (PEG200) produced the xanthohumol nanoemulsion with a loading capacity of 85.40 ± 0.33 g kg−1, mean droplet diameter of 42.35 ± 0.06 nm, and zeta potential of −21.78 ± 0.18 mV.Xanthohumol nanoemulsion has better relative stability. The relative oral bioavailability of xanthohumol nanoemulsion was increased by 1.76 times. These results provide a theoretical basis for the application of nanoemulsion containing xanthohumol in food and pharmaceutical industry. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). Methods: This is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle. Results: Twenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better. Conclusions: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase. [ABSTRACT FROM AUTHOR]

Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53−/− murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers. [ABSTRACT FROM AUTHOR]

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 μg/mL), Artemia salina (6.25–400 μg/mL), Allium cepa (10, 50, and 100 μg/mL), comet assay (100, 200, and 500 μg/mL), cytokinesis-block micronucleus (100, 250, and 500 μg/mL), confocal microscopy for apoptosis quantification (100 and 500 μg/mL), hemolysis and Saccharomyces cerevisiae central disk test (10, 35, and 75 μg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16–F10 cells rather than macrophages. For A. salina test, alpha-terpineol showed LC50 of 68.29 and 76.36 μg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 μg/mL, but it caused neither hemolysis, oxidative damage on the S. cerevisiae nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells. [ABSTRACT FROM AUTHOR]

In this work, we show the in vitro anticancer potential of surgical wires, obtained from zinc (ZnMg0.004) or magnesium (MgCa0.7) alloys by spatial technology comprising casting, extrusion, and final drawing processes. We also present the selective anticancer effects of applied soluble multilayer nanocoatings of zinc and magnesium onto titanium surfaces using the pulse laser deposition method. In the latter, the titanium samples were produced via 3D printing using the selective laser melting method and coated with various combinations of zinc and magnesium layers. For cytotoxicity studies, human dental pulp-derived stem cells (hDPSCs) and human osteosarcoma SaOS-2 cell line were used as representatives of healthy and cancer cells. Cells were examined against the 0.3–3.0 cm2/mL material extract ratios obtained from experimental and steel surgical wires, the latter being the current clinical industry standard. The MgCa0.7 alloy wires were approx. 1.5 times more toxic to cancer cells at all examined extract ratios vs. the extracts from steel surgical wires that exhibited comparable toxicity towards healthy and cancer cells. The ZnMg0.004 alloy wires displayed increased toxicity towards cancer cells with decreasing extract ratios. This was also reflected in the increased anticancer effectiveness, calculated based on the viability ratio of healthy cells to cancer cells, from 1.1 to 4.0 times. Healthy cell viability remained at 80–100%, whereas cancer cell survival fluctuated at 20–75%, depending on the extract ratio. Furthermore, the culture of normal or cancer cells on the surface of Zn/Mg-coated titanium allowed us to select combinations of specific coating layers that yielded a comparable anticancer effectiveness to that observed with the experimental wires that ranged between 2 and 3. Overall, this work not only demonstrates the substantial anticancer properties of the studied wires but also indicates that similar anticancer effects can be replicated with appropriate nanocoatings on titanium samples. We believe that this work lays the groundwork for the future potential development of the category of new implants endowed with anticancer properties. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of death worldwide, often resulting from uncontrolled growth in various organs. Protein kinase inhibitors represent an important class of targeted cancer therapies. Recently, the kinases BRAF and VEGFR-2 have shown synergistic effects on tumor progression. Seeking to develop dual BRAF/VEGFR-2 inhibitors, we synthesized 18 amino-benzothiazole derivatives with structural similarities to reported dual inhibitors. Four compounds—4a, 4f, 4l, and 4r—demonstrated remarkable cytotoxicity, with IC50 values ranging from 3.58 to 15.36 µM, against three cancer cell lines. Furthermore, these compounds showed IC50 values of 38.77–66.22 µM in the case of a normal cell line, which was significantly safer than the reference, sorafenib. Subsequent investigation revealed that compound 4f exhibited the capacity to inhibit the BRAF and VEGFR-2 enzymes, with IC50 values similar to sorafenib (0.071 and 0.194 µM, respectively). Moreover, compound 4f caused G2-M- and S-phase cycle arrest. Molecular modeling demonstrated binding patterns compatible with inhibition for both targets, where 4f exerted the critical interactions in the BRAF site and interacted in the VEGFR-2 site in a manner akin to sorafenib, demonstrating affinity similar to dabrafenib. [ABSTRACT FROM AUTHOR]

A short 19 bp dsRNA with 3′-trinucleotide overhangs acting as immunostimulating RNA (isRNA) demonstrated strong antiproliferative action against cancer cells, immunostimulatory activity through activation of cytokines and Type-I IFN secretion, as well as anti-tumor and anti-metastatic effects in vivo. The aim of this study was to determine the tolerance of chemical modifications (2′-F, 2′-OMe, PS, cholesterol, and amino acids) located at different positions within this isRNA to its ability to activate the innate immune system. The obtained duplexes were tested in vivo for their ability to activate the synthesis of interferon-α in mice, and in tumor cell cultures for their ability to inhibit their proliferation. The obtained data show that chemical modifications in the composition of isRNA have different effects on its individual functions, including interferon-inducing and antiproliferative effects. The effect of modifications depends not only on the type of modification but also on its location and the surrounding context of the modifications. This study made it possible to identify leader patterns of modifications that enhance the properties of isRNA: F2/F2 and F2_S/F2 for interferon-inducing activity, as well as F2_S5/F2_S5, F2-NH2/F2-NH2, and Ch-F2/Ch-F2 for antiproliferative action. These modifications can improve the pharmacokinetic and pharmacodynamic properties, as well as increase the specificity of isRNA action to obtain the desired effect. [ABSTRACT FROM AUTHOR]

Quinoxaline compounds are widely used in the fields of medicine and chemical industry, especially in the development of anticancer drugs, due to their significant biological activity. 6-fluoro-4-hydroxy-3-oxo-3,4-dihydroquinoline-1 (2H)-carboxylic acid tert-butyl ester was synthesized through a four-step reaction method in this paper, and its single crystal was obtained by solution crystallization method. Crystallographic analysis indicates that the compound belongs to monoclinic crystal system with space group C2/c, the unit cell dimensions are a =1.286 63(10) nm, b =2.252 49(17) nm, c =1.015 64(7) nm, Z =8, ρc =1. 359 g·cm-3, R =0. 053 8, Rw =0. 140 6. The optimal structure was calculated using density functional theory (DFT) in B3LYP/6-311 + G (2d, p) mode. The results are basically consistent with those obtained by X-ray single crystal diffraction. The antitumor activity study shows that the compound has good antitumor effect. In addition, the electrostatic potential and frontier molecular orbitals of the molecules were calculated by DFT to further understand their physical and chemical properties. [ABSTRACT FROM AUTHOR]

The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients. [ABSTRACT FROM AUTHOR]

The main goal of this study was to introduce a nanohybrid based on graphene oxide and zinc oxide with strong antitumor activity for the treatment of hepatitis B virus-associated hepatocarcinoma. In this regard, the nanohybrid was fabricated through the first attachment of locust bean gum chains on the graphene oxide surface and subsequently zinc oxide nanoparticles decorated on the surface of graphene oxide-locust bean gum nanosheets. Then, the prepared ternary nanohybrid was assessed in terms of physicochemical and microstructural characteristics, cytotoxicity, and antitumor activity. Our primary results indicated the successful fabrication of nanohybrids. The results of toxicity assays showed that the prepared nanohybrid represented higher cytotoxicity on the cancer cell line compared to the normal cells. Antitumor activity results demonstrated that the synthesized nanohybrid can superiorly decline viral and cellular oncogenes and induce cell apoptosis in liver cancer cells. In conclusion, the fabricated nanohybrid demonstrated strong antitumor activity against hepatocarcinoma cells, which can be considered a promising candidate for the treatment of hepatocarcinoma. [ABSTRACT FROM AUTHOR]

Two polyamine-diarylidenyl piperidone (DAP) derivatives, dimer polyamine-H-4073 and tetrameric polyamine-H-4073, were designed and synthesized as antitumor agents by coupling the bifluoro-substituted DAP STAT3 inhibitor H-4073 to two different polyamines through the binary fatty acid chains, respectively. MTT assay and a SW480 xenograft model identified dimer polyamine-H-4073 as good candidate antitumor agent with good efficacy, limited toxicity, and low resistance, in comparison with H-4073, cisplatin, and doxorubicin. Western blot analysis results indicated that dimer polyamine-H-4073 exhibited effectively inhibition on signal transducer and activator of transcription 3 (STAT3), indicating that it may be a STAT3 inhibitor. [ABSTRACT FROM AUTHOR]

CD98, also known as SLC3A2, is a multifunctional cell surface molecule consisting of amino acid transporters. CD98 is ubiquitously expressed in many types of tissues, but expressed at higher levels in cancerous tissues than in normal tissues. CD98 is also upregulated in most hepatocellular carcinoma (HCC) patients; however, the function of CD98 in HCC cells has been little studied. In this study, we generated a panel of monoclonal antibodies (MAbs) against surface proteins on human embryonic stem cells (hESCs). NPB15, one of the MAbs, bound to hESCs and various cancer cells, including HCC cells and non-small cell lung carcinoma (NSCLC) cells, but not to peripheral blood mononuclear cells (PBMCs) and primary hepatocytes. Immunoprecipitation and mass spectrometry identified the target antigen of NPB15 as CD98. CD98 depletion decreased cell proliferation, clonogenic survival, and migration and induced apoptosis in HCC cells. In addition, CD98 depletion decreased the expression of cancer stem cell (CSC) markers in HCC cells. In tumorsphere cultures, the expression of CD98 interacting with NPB15 was significantly increased, as were known CSC markers. After cell sorting by NPB15, cells with high expression of CD98 (CD98-high) showed higher clonogenic survival than cells with low expression of CD98 (CD98-low) in HCC cells, suggesting CD98 as a potential CSC marker on HCC cells. The chimeric version of NPB15 was able to induce antibody-dependent cellular cytotoxicity (ADCC) against HCC cells in vitro. NPB15 injection showed antitumor activity in an HCC xenograft mouse model. The results suggest that NPB15 may be developed as a therapeutic antibody for HCC patients. [ABSTRACT FROM AUTHOR]

Potentilla kleiniana belongs to the family Rosaceae, which distributes in Central Asia, East Asia and Southeast Asia. In China, this plant is mainly found in east, south and southwest provinces. P. kleiniana has been prescribed for the treatment of various diseases in the field of traditional Chinese medicine, such as cough, fever, tuberculosis, mastitis, rheumatoid arthritis. Our previous study found that P. kleiniana had a certain cytotoxicity on tumor cells. The purpose of this paper was to investigate the chemical constituents of P. kleiniana and their cytotoxicity on tumor cells. The 60% ethanol extract of P. kleiniana were isolated by D-101 macroporous adsorptive resins, silica gel, Sephadex LH-20, Toyopearl HW-40F, semi-preparative high performance liquid chromatography and other methods, and their chemical structures were elucidated on the basis of physicochemical properties, NMR and HR-ESI-MS analysis. Meanwhile, all these compounds were evaluated for cytotoxicity against human cervical cancer cell line Hela. The results were as follows: (1) Thirteen lignans were isolated and identified as (+)-pionresinol (1), (+)-8-hydroxypinoresinol (2), (+)-syringaresinol (3), (+)-medioresinol (4), (+)-pionresinol-4-O-β-D-glucopyranoside (5), (+)-8′-hydroxypinoresinol-4-O-β-D-glucopyranoside (6), (+)-8′-hydroxypinoresinol-4′-O-β-D-glucopyranoside (7), (+)-pinoresinol-8′-O-β-D-glucopyranoside (8), schilignan F (9), (+)-pionresinol-4, 4′-O-bisglucopyranoside (10), (+)-lariciresinol-4′-O-β-D-glucopyranoside (11), neoolivil-4-O-β-D-glucopyranoside (12), 3,3′-bis［3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran］(13). Among them, compounds 1-4, 7, 8, 10, 12, 13 were isolated from genus Potentilla for the first time, and compounds 5, 6, 9, 11 were isolated from P. kleiniana for the first time. (2) Cytotoxicity studies showed that compounds 1, 3 and 4 display certain inhibitory activities against Hela cells with IC50 values of (69.94 ± 1.89), (66.25 ± 2.11), (59.81 ± 1.73) μmol·L-1, respectively. Therefore, the study enriches the chemical constituents of P. kleiniana, and provides a material basis for the development of anti-cervical cancer drugs.

Abstract Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments. Furthermore, dedifferentiation can occur providing relapse of the disease. In this study we evaluated fenretinide, a semisynthetic ATRA derivative, encapsulated in nanomicelles (nano-fenretinide) as an alternative treatment to ATRA in APL. Nano-fenretinide was prepared by fenretinide encapsulation in a self-assembling phospholipid mixture. Physico-chemical characterization was carried out by dinamic light scattering and spectrophotometry. The biological activity was evaluated by MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Nano-fenretinide induced apoptosis in acute promyelocytic leukemia cells (HL60) by an early increase of reactive oxygen species and a mitochondrial potential decrease. The fenretinide concentration that induced 90–100% decrease in cell viability was about 2.0 µM at 24 h, a concentration easily achievable in vivo when nano-fenretinide is administered by oral or intravenous route, as demonstrated in previous studies. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA.

Abstract Sugar esters display surface-active properties, wetting, emulsifying, and other physicochemical phenomena following their amphipathic nature and recognize distinct biological activity. The development of nutritional pharmaceuticals and other applications remains of great interest. Herein, three novel homologous series of several N-mono-fatty acyl amino acid glucosyl esters were synthesized, and their physicochemical properties and biological activities were evaluated. The design and preparation of these esters were chemically performed via the reaction of glucose with different fatty acyl amino acids as renewable starting materials, with the suggestion that they would acquire functional characteristics superior and competitive to certain conventional surfactants. The synthesized products are characterized using FTIR, 1H-NMR, and 13C-NMR spectroscopy. Further, their physicochemical properties, such as HLB, CMC, Γmax, γCMC, and Amin, were determined. Additionally, their antimicrobial and anticancer efficiency were assessed. The results indicate that the esters' molecular structure, including the acyl chain length and the type of amino acid, significantly influences their properties. The measured HLB ranged from 8.84 to 12.27, suggesting their use as oil/water emulsifiers, wetting, and cleansing agents. All esters demonstrate promising surface-active characteristics, with moderate to high foam production with good stability. Notably, compounds 6-O-(N-dodecanoyl, tetradecanoyl cysteine)-glucopyranose (34, 35), respectively and 6-O-(N-12-hydroxy-9-octadecenoyl cysteine)-glucopyranose (38) display superior foamability. Wetting efficiency increased with decreasing the chain length of the acyl group. The storage results reveal that increasing the fatty acyl hydrophobe length enhances the derived emulsion's stability for up to 63 days. Particularly, including cysteine in these glucosyl esters improves wetting, foaming, and emulsifying potentialities. Furthermore, the esters exhibit antibacterial activity against several tested Gram-positive and Gram-negative bacteria and fungi. On the other hand, they show significant antiproliferative effects on some liver tumor cell lines. For instance, compounds 6-O-(N-12-hydroxy-9-octadecenoylglycine)-glucopyranose (28), 6-O-(N-dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoylvaline)- glucopyranose (29, 31, 32 and 33), respectively in addition to the dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoyl cysteine glucopyranose (34, 36, 37 and 38), respectively significantly inhibit the examined cancer cells.

Abstract The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel’s therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects. Graphical Abstract

Ewelina Waglewska,1 Julita Kulbacka,2,3 Urszula Bazylinska1 1Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland; 2Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Wroclaw, Poland; 3State Research Institute Centre for Innovative Medicine, Department of Immunology and Bioelectrochemistry, Vilnius, LithuaniaCorrespondence: Urszula Bazylinska, Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, Wroclaw, 50-370, Poland, Tel +48 713202183, Email urszula.bazylinska@pwr.edu.plPurpose: Numerous failures in melanoma treatment as a highly aggressive form of skin cancer with an unfavorable prognosis and excessive resistance to conventional therapies are prompting an urgent search for more effective therapeutic tools. Consequently, to increase the treatment efficiency and to reduce the side effects of traditional administration ways, herein, it has become crucial to combine photodynamic therapy as a promising therapeutic approach with the selectivity and biocompatibility of a novel colloidal transdermal nanoplatform for effective delivery of hybrid cargo with synergistic effects on melanoma cells.Methods: The self-assembled bilosomes, co-stabilized with L-α-phosphatidylcholine, sodium cholate, Pluronic® P123, and cholesterol, were designated, and the stability of colloidal vesicles was studied using dynamic and electrophoretic light scattering, also provided in cell culture medium (Dulbecco’s Modified Eagle’s Medium). The hybrid compounds – a classical photosensitizer (Methylene Blue) along with a complementary natural polyphenolic agent (curcumin), were successfully co-loaded, as confirmed by UV-Vis, ATR-FTIR, and fluorescent spectroscopies. The biocompatibility and usefulness of the polymer functionalized bilosome with loaded double cargo were demonstrated in vitro cyto- and phototoxicity experiments using normal keratinocytes and melanoma cancer cells.Results: The in vitro bioimaging and immunofluorescence study upon human skin epithelial (A375) and malignant (Me45) melanoma cell lines established the protective effect of the PEGylated bilosome surface. This effect was confirmed in cytotoxicity experiments, also determined on human cutaneous (HaCaT) keratinocytes. The flow cytometry experiments indicated the enhanced uptake of the encapsulated hybrid cargo compared to the non-loaded MB and CUR molecules, as well as a selectivity of the obtained nanocarriers upon tumor cell lines. The phyto-photodynamic action provided 24h-post irradiation revealed a more significant influence of the nanoplatform on Me45 cells in contrast to the A375 cell line, causing the cell viability rate below 20% of the control.Conclusion: As a result, we established an innovative and effective strategy for potential metastatic melanoma treatment through the synergism of phyto-photodynamic therapy and novel bilosomal-origin nanophotosensitizers. Keywords: nanovesicular carriers, human melanoma, A375 cells, Me45 cells, antitumor activity, phyto-photodynamic therapy

Abstract Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments. Furthermore, dedifferentiation can occur providing relapse of the disease. In this study we evaluated fenretinide, a semisynthetic ATRA derivative, encapsulated in nanomicelles (nano-fenretinide) as an alternative treatment to ATRA in APL. Nano-fenretinide was prepared by fenretinide encapsulation in a self-assembling phospholipid mixture. Physico-chemical characterization was carried out by dinamic light scattering and spectrophotometry. The biological activity was evaluated by MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Nano-fenretinide induced apoptosis in acute promyelocytic leukemia cells (HL60) by an early increase of reactive oxygen species and a mitochondrial potential decrease. The fenretinide concentration that induced 90–100% decrease in cell viability was about 2.0 µM at 24 h, a concentration easily achievable in vivo when nano-fenretinide is administered by oral or intravenous route, as demonstrated in previous studies. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA. [ABSTRACT FROM AUTHOR]

The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(H2O)](H2O)2 (I) and [(acr)H][VO(nta)(H2O)](H2O)2 (II), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts—1,10-phenanthrolinium, [(phen)H][VO(nta)(H2O)](H2O)0.5 (III), 2,2′-bipyridinium [(bpy)H][VO(nta)(H2O)](H2O) (IV), and two newly synthesized compounds (I) and (II)—were evaluated against prostate cancer (PC3) and breast cancer (MCF-7) cells. All the compounds exhibited strong cytotoxic effects on cancer cells and normal cells (HaCaT human keratinocytes). The structure–activity relationship analysis revealed that the number and arrangement of conjugated aromatic rings in the counterion had an impact on the antitumor effect. The compound (III), the 1,10-phenanthrolinium analogue, exhibited the greatest activity, whereas the acridinium salt (II), with a different arrangement of three conjugated aromatic rings, showed the lowest toxicity. The increased concentrations of the compounds resulted in alterations to the cell cycle distribution with different effects in MCF-7 and PC3 cells. In MCF-7 cells, compounds I and II were observed to block the G2/M phase, while compounds III and IV were found to arrest the cell cycle in the G0/G1 phase. In PC3 cells, all compounds increased the rates of cells in the G0/G1 phase. [ABSTRACT FROM AUTHOR]

Sugar esters display surface-active properties, wetting, emulsifying, and other physicochemical phenomena following their amphipathic nature and recognize distinct biological activity. The development of nutritional pharmaceuticals and other applications remains of great interest. Herein, three novel homologous series of several N-mono-fatty acyl amino acid glucosyl esters were synthesized, and their physicochemical properties and biological activities were evaluated. The design and preparation of these esters were chemically performed via the reaction of glucose with different fatty acyl amino acids as renewable starting materials, with the suggestion that they would acquire functional characteristics superior and competitive to certain conventional surfactants. The synthesized products are characterized using FTIR, 1H-NMR, and 13C-NMR spectroscopy. Further, their physicochemical properties, such as HLB, CMC, Γmax, γCMC, and Amin, were determined. Additionally, their antimicrobial and anticancer efficiency were assessed. The results indicate that the esters' molecular structure, including the acyl chain length and the type of amino acid, significantly influences their properties. The measured HLB ranged from 8.84 to 12.27, suggesting their use as oil/water emulsifiers, wetting, and cleansing agents. All esters demonstrate promising surface-active characteristics, with moderate to high foam production with good stability. Notably, compounds 6-O-(N-dodecanoyl, tetradecanoyl cysteine)-glucopyranose (34, 35), respectively and 6-O-(N-12-hydroxy-9-octadecenoyl cysteine)-glucopyranose (38) display superior foamability. Wetting efficiency increased with decreasing the chain length of the acyl group. The storage results reveal that increasing the fatty acyl hydrophobe length enhances the derived emulsion's stability for up to 63 days. Particularly, including cysteine in these glucosyl esters improves wetting, foaming, and emulsifying potentialities. Furthermore, the esters exhibit antibacterial activity against several tested Gram-positive and Gram-negative bacteria and fungi. On the other hand, they show significant antiproliferative effects on some liver tumor cell lines. For instance, compounds 6-O-(N-12-hydroxy-9-octadecenoylglycine)-glucopyranose (28), 6-O-(N-dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoylvaline)- glucopyranose (29, 31, 32 and 33), respectively in addition to the dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoyl cysteine glucopyranose (34, 36, 37 and 38), respectively significantly inhibit the examined cancer cells. [ABSTRACT FROM AUTHOR]

Despite significant progress made over the past two decades in the treatment of chronic myeloid leukemia (CML), there is still an unmet need for effective and safe agents to treat patients with resistance and intolerance to the drugs used in clinic. In this work, we designed 2-arylaminopyrimidine amides of isoxazole-3-carboxylic acid, assessed in silico their inhibitory potential against Bcr-Abl tyrosine kinase, and determined their antitumor activity in K562 (CML), HL-60 (acute promyelocytic leukemia), and HeLa (cervical cancer) cells. Based on the analysis of computational and experimental data, three compounds with the antitumor activity against K562 and HL-60 cells were identified. The lead compound efficiently suppressed the growth of these cells, as evidenced by the low IC50 values of 2.8 ± 0.8 μM (K562) and 3.5 ± 0.2 μM (HL-60). The obtained compounds represent promising basic structures for the design of novel, effective, and safe anticancer drugs able to inhibit the catalytic activity of Bcr-Abl kinase by blocking the ATP-binding site of the enzyme. [ABSTRACT FROM AUTHOR]

Objective: Dehydroepiandrosterone plays an important role in the human beings due to its ability to be converted into androgens and oestrogens. The aim of this paper is to synthesize a series of novel dehydroepiandrosteronyl 1,2,3-triazole derivatives and study the antitumor activity of the synthesized compounds. Methods: Novel dehydroepiandrosteronyl 1,2,3-triazole derivatives were synthesized across the Mitsunobu and click reaction, respectively. The cytotoxicities of the synthesized compounds against HeLa, HGC-27, and HEK-293T cells were determined by MTT assay. Results and Discussion: The results showed that compound (V) (3R,8R,9S,10R,13S,14S)3-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro17H-cyclopenta[a]phenanthren-17-one had better inhibitory activity against the tumor cell lines tested. The IC50 value of inhibitory activity on human cervical cancer cell (HeLa) and human gastric cancer cell (HGC-27) was 33.6 and 22.3 μmolL–1, respectively. Conclusions: This work provides useful strategies for the design and synthesis of new steroidal antitumor drugs. The synthesized compounds have certain inhibitory activity on tumor cell growth and proliferation, but have little damage on normal cells, which deserves further study. [ABSTRACT FROM AUTHOR]

Potentilla kleiniana belongs to the family Rosaceae, which distributes in Central Asia, East Asia and Southeast Asia. In China, this plant is mainly found in east, south and southwest provinces. P. kleiniana has been prescribed for the treatment of various diseases in the field of traditional Chinese medicine, such as cough, fever, tuberculosis, mastitis, rheumatoid arthritis. Our previous study found that P. kleiniana had a certain cytotoxicity on tumor cells. The purpose of this paper was to investigate the chemical constituents of P. kleiniana and their cytotoxicity on tumor cells. The 60% ethanol extract of P. kleiniana were isolated by D-101 macroporous adsorptive resins, silica gel, Sephadex LH-20, Toyopearl HW-40F, semi-preparative high performance liquid chromatography and other methods, and their chemical structures were elucidated on the basis of physicochemical properties, NMR and HR-ESI-MS analysis. Meanwhile, all these compounds were evaluated for cytotoxicity against human cervical cancer cell line Hela. The results were as follows:(1)Thirteen lignans were isolated and identified as(+)-pionresinol(1),(+)-8-hydroxypinoresinol(2),(+)-syringaresinol(3),(+)-medioresinol(4),(+)-pionresinol-4-O-β-D-glucopyranoside(5),(+)-8'-hydroxypinoresinol-4-O-β-D-glucopyranoside(6),(+)-8'-hydroxypinoresinol-4'-O-β-D-glucopyranoside(7),(+)-pinoresinol-8'-O-β-D-glucopyranoside(8), schilignan F(9),(+)-pionresinol-4, 4'-O-bisglucopyranoside(10),(+)-lariciresinol-4'-O-β-D-glucopyranoside(11), neoolivil-4-O-β-D-glucopyranoside(12), 3,3'-bis [3,4-dihydro-4-hydroxy-6-methoxy-2H-1-benzopyran](13). Among them, compounds 1-4, 7, 8, 10, 12, 13 were isolated from genus Potentilla for the first time, and compounds 5, 6, 9, 11 were isolated from P. kleiniana for the first time.(2)Cytotoxicity studies showed that compounds 1, 3 and 4 display certain inhibitory activities against Hela cells with IC50 values of(69.94 ± 1.89),(66.25 ± 2.11),(59.81 ± 1.73)μmol·L-1, respectively. Therefore, the study enriches the chemical constituents of P. kleiniana, and provides a material basis for the development of anti-cervical cancer drugs. [ABSTRACT FROM AUTHOR]

Interleukin 2, also known as T cell growth factor, brought a great revolution in the field of immunology. IL-2 is a pleiotropic cytokine and one of the cytokines that is approved by FDA for cancer immunotherapy particularly kidney and skin cancer. Interleukin-2 (IL-2) is a 4-helix-bundle type I cytokine possessing a cytokine receptor chain essential for the immune response. The current study presents a vector/host combination (pET28a(+)/IL-2) and optimization of expression in LB, TB and M9 media with varying concentrations of inducers (IPTG and lactose) and post induction time. Maximum expression of IL-2 was achieved in LB with 0.5 mM IPTG for 6 hours post induction time. A denaturing purification scheme (Immobilized metal affinity chromatography) was employed for the purification of IL-2. The refolding of the purified IL-2 was achieved by stepwise dialysis method using urea gradient (8M-0M). Human IL-2 was recovered from 1 litre culture to a purity level of ~95%. In vitro cytotoxic potential of IL-2 on HepG-2 and MCF-7 cell lines revealed that it possess sufficient cytotoxic potential and can inhibit the growth of these cell lines directly. Thus, refolded IL-2 had activity identical to that of authentic IL-2 and enhanced the anti-tumor activity of HepG-2 as compared to MCF-7 cells. These conclusions suggest the potential use of the refolded cytokine as immunotherapeutic agent for treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel's therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects. [ABSTRACT FROM AUTHOR]

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum spore powder, valued for its nutritional and medicinal properties, contains polysaccharides crucial for its efficacy. However, the complex structural nature of these polysaccharides necessitates further investigation to fully realize their potential. This study aimed to investigate the effects of acid heat treatment on Ganoderma lucidum spore polysaccharides (GLSPs) to enhance their properties and application in antitumor activity. The GLSP was obtained via acid heat treatment, concentration, and centrifugal separation. This process led to a notable reduction in polysaccharide molecular weight, increasing water solubility and bioavailability. Analytical techniques including NMR spectroscopy and methylation analysis revealed a polysaccharide composition comprising four distinct monosaccharides, with molecular weights of 3291 Da (Mw) and 3216 Da (Mn). Six different linkage modes were identified, with a molar ratio of 1:5:2:3:4:3. In vivo experiments demonstrated the GLSP's significant inhibitory effect on the growth of four tumor models (sarcoma S180, Lewis lung cancer, liver cancer H22, and colon cancer C26) in mice, with no observed toxicity. These findings suggest the GLSP's potential as an antitumor therapeutic agent for clinical use. [ABSTRACT FROM AUTHOR]

Regulatory proteins involved in human cellular division and proliferation, cyclin-dependent kinases 4 and 6 (CDK4/6) are overexpressed in numerous cancers, including triple-negative breast cancer (TNBC). TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis, and has a single treatment method. As one of the CDK4/6 inhibitors, abemaciclib can effectively inhibit the growth of breast tumors. In this study, we synthesized LA-D-B1, a derivative of Abemaciclib, and investigated its anti-tumor effects in breast cancer. Methods: Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cloning and migration abilities were determined by colony formation assay and wound healing assay. Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay. The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting, which quantified the levels of proteins associated with the cyclin-dependent kinase (CDK) 4/6-cyclin D-Rb-E2F pathway. The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane (CAM) model. Results: The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation, induced apoptosis, and caused cell cycle arrest. Furthermore, LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway, including CDK4, CDK6 and E2F1. The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model. Conclusion: In this study, LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer. These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer. [ABSTRACT FROM AUTHOR]

In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial fields. This study aims to synthetise two series of methylimidazolium ILs bearing long alkyl chain in their cations (C9, C10, C12, C14, C16, C18, C20) and with tetrafluoroborate (BF4) and the 1,3-dimethyl-5-sulfoisophthalate (DMSIP) as counter ions. The ILs were characterised using 1H-NMR and MALDI-TOF, and their thermal behaviour was investigated through DSC and TGA. Additionally, the antimicrobial, anticancer, and cytotoxic activities of the ILs were analysed. Moreover, the most promising ILs were incorporated at different concentrations (0.5, 1, 5 wt%) into polyvinyl chloride (PVC) by solvent casting to obtain antimicrobial blend films. The thermal properties and stability of the resulting PVC/IL films, along with their hydrophobicity/hydrophilicity, IL surface distribution, and release, were studied using DSC and TGA, contact angle (CA), SEM, and UV–vis spectrometry, respectively. Furthermore, the antimicrobial and cytotoxic properties of blends were analysed. The in vitro results demonstrated that the antimicrobial and antitumor activities of pure ILs against t Listeria monocytogenes, Escherichia coli, Pseudomonas fluorescens strains, and the breast cancer cell line (MCF7), respectively, were mainly dependent on their structure. These activities were higher in the series containing the BF4 anion and increased with the increase in the methylimidazolium cation alkyl chain length. However, the elongation of the alkyl chain beyond C16 induced a decrease in antimicrobial activity, indicating a cut-off effect. A similar trend was also observed in terms of in vitro biocompatibility. The loading of both the series of ILs into the PVC matrix did not affect the thermal stability of PVC blend films. However, their Tonset decreased with increased IL concentration and alkyl chain length. Similarly, both the series of PVC/IL films became more hydrophilic with increasing IL concentration and alkyl chain. The loading of ILs at 5% concentration led to considerable IL accumulation on the blend film surfaces (as observed in SEM images) and, subsequently, their higher release. The biocompatibility assessment with healthy human dermal fibroblast (HDF) cells and the investigation of antitumoral properties unveiled promising pharmacological characteristics. These findings provide strong support for the potential utilisation of ILs in biomedical applications, especially in the context of cancer therapy and as antibacterial agents to address the challenge of antibiotic resistance. Furthermore, the unique properties of the PVC/IL films make them versatile materials for advancing healthcare technologies, from drug delivery to tissue engineering and antimicrobial coatings to diagnostic devices. [ABSTRACT FROM AUTHOR]

New Co (II), Ni (II), and Cu (II) complexes based on ρ‐dimethylaminobenzaldehyde thiosemicarbazone (DABT) as chelating agents were synthesized. The structure of the three complexes was determined by elemental analysis and TGA with IR, UV–Vis, XRD, ESR spectra, conductivity, and magnetic measurements. It was found that the isolated DABT complexes have tetrahedral structure with a neutral nature. The antitumor activity of DABT complexes using viability assay was examined against hepatocellular carcinoma cell lines (HepG‐2). The DABT complexes have moderate activity with respect to the standard drugs. DABT–Ni (II) complex has higher antitumor activity (IC50 = 12 μM) than the other DABT complexes. In addition, a molecular docking study was performed for DABT and its complexes to investigate their therapeutic features as topoisomerase inhibitors. It is clear that the most effective compound was DABT–Ni (II) complex to bind to 3QX3. Also, density functional theory calculations with the structure–activity relationship were computed for DABT and its complexes using the Gaussian program. There was confirmation between the obtained theoretical data and the experimental studies. [ABSTRACT FROM AUTHOR]

Cancer is a disease that encompasses multiple and different malignant conditions and is among the leading causes of death in the world. Therefore, the search for new pharmacotherapeutic options and potential candidates that can be used as treatments or adjuvants to control this disease is urgent. Natural products, especially those obtained from plants, have played an important role as a source of specialized metabolites with recognized pharmacological properties against cancer, therefore, they are an excellent alternative to be used. The objective of this research was to evaluate the action of the monoterpene isoespintanol (ISO) against the human tumor cell lines MDA-MB-231, A549, DU145, A2780, A2780-cis and the non-tumor line MRC-5. Experiments with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescence with propidium iodide (PI), 4′,6-diamidino-2-phenylindole dilactate (DAPI) and green plasma revealed the cytotoxicity of ISO against these cells; furthermore, morphological and chromogenic studies revealed the action of ISO on cell morphology and the inhibitory capacity on reproductive viability to form colonies in MDA-MB-231 cells. Likewise, 3D experiments validated the damage in these cells caused by this monoterpene. These results serve as a basis for progress in studies of the mechanisms of action of these compounds and the development of derivatives or synthetic analogues with a better antitumor profile. [ABSTRACT FROM AUTHOR]

Bacterial infection poses a grave peril to human existence and well‐being, particularly with the emergence of drug‐resistant bacteria, leading to an alarming rise in the incidence of severe illness and mortality. Antimicrobial photodynamic therapy (aPDT) has emerged as one of the most promising strategies for combating bacterial infections due to its potent bactericidal efficacy and non‐inducement of resistance. The development of novel photosensitizers represents a viable approach to further enhance the efficacy of aPDT. Hence, the structural design and application strategies of phthalocyanine‐based photosensitizers were summarized to provide guidance in the development of highly efficient aPDT agents. [ABSTRACT FROM AUTHOR]

Heterocyclic compounds such as pyrrole and pyrrolidine derivatives have a broad spectrum of biological activity, being widely used as pharmacophore to design novel bioactive compounds. In this work, sixteen pyrrole and pyrrolidine derivatives were synthesized and evaluated for their growth inhibitory activity on two human cancer cells lines: breast cancer MDA‐MB‐231 and chronic myelogenous leukemia (K562). Eight compounds showed activity against at least one tumor cell line (IC50=49.15–195.9 μM). The compounds were tested in non‐cancerous human lung fibroblasts WI‐26VA4 to evaluate their selectivity index. In addition, Hierarchical Cluster Analysis (HCA) studies were carried out in attempt to establish a structure‐activity relationship. [ABSTRACT FROM AUTHOR]

This research's scope encompassed biotechnological, phytochemical, and biological studies of Schisandra henryi, including investigations into its in vitro microshoot culture grown in PlantForm bioreactors (temporary immersion systems, TISs), as well as extracts from leaves of the parent plant, focusing on anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. The phytochemical analysis included the isolation and quantification of 17 compounds from dibenzocyclooctadiene, aryltetralin lignans, and neolignans using centrifugal partition chromatography (CPC), HPLC-DAD, and UHPLC-MS/MS tandem mass spectrometry with triple quadrupole mass filter methods. Higher contents of compounds were found in microshoots extracts (max. 543.99 mg/100 g DW). The major compound was schisantherin B both in the extracts from microshoots and the leaves (390.16 and 361.24 mg/100 g DW, respectively). The results of the anti-inflammatory activity in terms of the inhibition of COX-1, COX-2, sPLA2, and LOX-15 enzymes indicated that PlantForm microshoot extracts showed strong activity against COX-1 and COX-2 (for 177 mg/mL the inhibition percentage was 76% and 66%, respectively). The antioxidant potential assessed using FRAP, CUPRAC, and DPPH assays showed that extracts from microshoot cultures had 5.6, 3.8, and 3.3 times higher power compared to extracts from the leaves of the parent plant, respectively. The total polyphenol content (TPC) was 4.1 times higher in extracts from the in vitro culture compared to the leaves. The antiproliferative activity against T-cell lymphoblast line Jurkat, breast adenocarcinoma cultures (MCF-7), colon adenocarcinoma (HT-29), and cervical adenocarcinoma (HeLa), showed that both extracts have considerable effects on the tested cell lines. The antimicrobial activity tested against strains of Gram-positive and Gram-negative bacteria and fungi showed the highest activity towards H. pylori (MIC and MBC 0.625 mg/mL). [ABSTRACT FROM AUTHOR]

Deep eutectic solvents (DESs) are novel solvents with physicochemical properties similar to those of ionic liquids, and they have attracted extensive attention for the extraction of bioactive compounds from different plant materials in the context of green chemistry and sustainable development. In this study, seven DESs with different polarities were explored as green extraction solvents for cembratrien-diols (CBT-diols) from waste tobacco flowers. The best solvent, DES-3 (choline chloride: lactic acid (1:3)), which outperformed conventional solvents (methanol, ethanol, and ethyl acetate), was selected and further optimized for microwave-assisted DES extraction using the response surface methodology. The maximum yield of CBT-diols (6.23 ± 0.15 mg/g) was achieved using a microwave power of 425 W, microwave time of 32 min, solid/liquid ratio of 20 mg/mL, and microwave temperature of 40 °C. Additionally, the isolated CBT-diols exhibited strong antimicrobial activity against Salmonella, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa and antitumor activity in the human liver cancer HepG2 and SMMC-7721 cell lines. This study highlights the feasibility of recovering CBT-diols from tobacco flower waste using DESs and provides opportunities for potential waste management using green technologies. [ABSTRACT FROM AUTHOR]

Objective: In order to enrich the library of anti-tumor small molecule compounds, 8 compounds, with highly effective antitumor, have been designed and synthesized. Methods: MTT assay was used to detect the antiproliferation activity of 8 compounds on four human tumor cell lines (HCT-116, HeLa, DU-145, and SGC-7901). Cell cycle experiment, cell migration experiment, cell clone experiment and cell apoptosis experiment were used to study the antitumor mechanism of compound (V). Results: The compound (V) showed the strongest antitumor activity against the above four human tumor cells, especially against HCT-116 cells, with an IC50 value of 4.21 ± 0.39 μM, which was significantly lower than that of cyclophosphamide. The results of a variety of cell experiments showed that the compound (V) significant antitumor activity, such as inhibiting the proliferation and migration of HCT-116 cells, arresting HCT-116 cells at S phase, and inducing apoptosis in HCT-116 cells. Discussion: Slight changes in the R group can cause significant changes in the in vitro antitumor activity, and when R is a strong electron donor group of ethyl L-tyrosinate, compound (V) exhibits the strongest inhibitory effect, with an IC50 value of 4.21 ± 0.39 μM on HCT-116 cells. Conclusions: 8 compounds showed significant anti-tumor activity, and the compound (V), with a strong electron donor group of ethyl L-tyrosinate, showed the most significant effect, and the antiproliferation and antimigration effects of compound (V) was further investigated. [ABSTRACT FROM AUTHOR]