HepG2 Cancer Cells Research Articles

Five New C21 -Steroidal Sapogenins from the Acid Hydrolysate of Cynanchum otophyllum Roots.

Five new C21 -steroidal sapogenins (1-5) named cynotogenins J-N, were isolated from the acid hydrolysate of Cynanchum otophyllum roots. Their structures were established by extensive spectroscopic analysis (UV, IR, HR-ESI-MS, and NMR). Most notably, compounds 1-3 harboring a rare 5β,6β-epoxy group in the C21 -steroidal skeleton of Cynanchum plants. All compounds were evaluated for their cytotoxicities against multiple cancer cell lines, in which compounds 5 showed weak cytotoxicity against HepG2 cancer cells with IC50 values of 44.90 μM.

Photo-oxidase carbon dot-based nanozyme for breast cancer theranostics under normoxia condition

Ultra-small histidine-functionalized carbon nanodots (His C-dots) with engineered modality as photo-oxidative nanozymes for cancer theranostics were prepared by one step microwave-assisted pyrolysis. The role of chemically embedded imidazole ring into nanoparticle aromatic domains was to enhance the absorbance, fluorescence, and phosphorescence intensities in aqueous solution at room temperature. It contributed to the increase of pyrrolic nitrogen, which was responsible for the higher oxygen adsorption and better photosensitization under visible irradiation. The ability of nanozyme as theranostics was demonstrated on illuminated with visible light B16-F10 mouse melanoma cells with high metastatic potential under normoxic condition. The inhibition of cell migration was measured by wound healing assay after scratching confluent monolayer of the breast cancer cells. The microscopic data revealed that the metastatic migration could be controlled by the applied nanozyme dosage, which was responsible for the production of singlet oxygen and the causing of effective photo-induced cytotoxicity. The biocompatibility of the illuminated His C-dots was proved on ATPase activity of intact mitochondria and sub-mitochondrial particles, on diamine oxidase activity of liver and kidney fractions in dark mode, MTT assay as well as on non-illuminated adenocarcinomic human alveolar basal epithelial cells (A549) and human liver cancer cells (HepG2). The satisfactory ability of the reported nanoparticles as fluorescence anticancer agents makes them a promising platform for the development of oxidize-mimicking nanozymes with application in the photodynamic therapy.

Quantification of Xanthone and Anthocyanin in Mangosteen Peel by UPLC-MS/MS and Preparation of Nanoemulsions for Studying Their Inhibition Effects on Liver Cancer Cells

Mangosteen peel, a waste produced during mangosteen processing, has been reported to be rich in xanthone and anthocyanin, both of which possess vital biological activities such as anti-cancer properties. The objectives of this study were to analyze various xanthones and anthocyanins in mangosteen peel by UPLC-MS/MS for the subsequent preparation of both xanthone and anthocyanin nanoemulsions to study their inhibition effects on liver cancer cells HepG2. Results showed that methanol was the optimal solvent for the extraction of xanthones and anthocyanins, with a total amount of 68,543.39 and 2909.57 μg/g, respectively. A total of seven xanthones, including garcinone C (513.06 μg/g), garcinone D (469.82 μg/g), γ-mangostin (11,100.72 μg/g), 8-desoxygartanin (1490.61 μg/g), gartanin (2398.96 μg/g), α-mangostin (51,062.21 μg/g) and β-mangostin (1508.01 μg/g), as well as two anthocyanins including cyanidin-3-sophoroside (2889.95 μg/g) and cyanidin-3-glucoside (19.72 μg/g), were present in mangosteen peel. The xanthone nanoemulsion was prepared by mixing an appropriate portion of soybean oil, CITREM, Tween 80 and deionized water, while the anthocyanin nanoemulsion composed of soybean oil, ethanol, PEG400, lecithin, Tween 80, glycerol and deionized water was prepared as well. The mean particle size of the xanthone extract and nanoemulsion were, respectively, 22.1 and 14.0 nm as determined by DLS, while the zeta potential was -87.7 and -61.5 mV. Comparatively, xanthone nanoemulsion was more effective than xanthone extract in inhibiting the growth of HepG2 cells, with the IC50 being 5.78 μg/mL for the former and 6.23 μg/mL for the latter. However, the anthocyanin nanoemulsion failed to inhibit growth of HepG2 cells. Cell cycle analysis revealed that the proportion of the sub-G1 phase followed a dose-dependent increase, while that of the G0/G1 phase showed a dose-dependent decline for both xanthone extracts and nanoemulsions, with the cell cycle being possibly arrested at the S phase. The proportion of late apoptosis cells also followed a dose-dependent rise for both xanthone extracts and nanoemulsions, with the latter resulting in a much higher proportion at the same dose. Similarly, the activities of caspase-3, caspase-8 and caspase-9 followed a dose-dependent increase for both xanthone extracts and nanoemulsions, with the latter exhibiting a higher activity at the same dose. Collectively, xanthone nanoemulsion was more effective than xanthone extract in inhibiting the growth of HepG2 cells. Further research is needed to study the anti-tumor effect in vivo.

Biogenic Mg doped CeO2 nanoparticles via Hibiscus sabdariffa and its potential biological applications

Cancer and inflammation are important challenges and leading causes of death worldwide. Development of nanomaterial based therapeutic compounds obtained from natural products is thought to be a pillar in drug discovery. The present research describes the cytotoxicity, anti-inflammatory and antioxidant activities of cerium oxide (CeO2) and magnesium (Mg) doped CeO2 nanoparticles (NPs). Hibiscus sabdariffa (HS) flower extract is used to bio-fabricate Mg doped CeO2 nanoparticles in an eco-friendly and cost-effective manner. The morphological and structural characteristics of the bioengineered CeO2 and Mg doped CeO2 NPs were investigated using complementary characterization techniques, such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) equipped with Electron Dispersive X-rays Spectroscopy (EDS). SEM analysis showed that the NPs possess spherical shape and particle size of around 100 nm. The cytotoxicity results demonstrated that CeO2 and Mg doped CeO2 NPs caused potent toxicity on MCF-7, HepG2 and A-549 cancer cells. The highest toxicity was observed in A-549 cells with an IC50 = 79.19 ± 3.07 µg/mL and maximum cell inhibition of ~ 96%. Furthermore, Mg doped CeO2 NPs also depicted DPPH and H2O2 scavenging potential with maximum % of inhibition = 79.43 ± 1.51 and 72.43 ± 1.51 respectively at 1000 µg/mL. Interestingly, these NPs inhibited inflammatory markers, COX-1 enzyme with IC50 = 25.98 ± 1.76 µg/mL and protein denaturation with IC50= 14.85 ± 0.97 µg/mL, respectively. The outcome of the present study revealed that the biosynthesized Mg doped CeO2 NPs using HS flower extract possess promising biomedical potential.

Oxygen-vacancy enhanced peroxidase-like activity of Cu–SnO2 for dual-mode sensing of hydrogen peroxide

Hydrogen peroxide (H2O2) is an important oxidant and one common active oxygen species in organisms. It is critically important to realize fast and accurate detection of H2O2. In this work, Cu–SnO2 is successfully evaluated as a dual mode-sensing material for H2O2 detection. The study proves that the peroxidase-like activity increases steadily with the oxygen vacancy concentration on the material surface. The material Cu–SnO2-1.5, which shows the highest amount of oxygen vacancy, successfully oxidizes colorless substrate (TMB) to blue (ox TMB) in the presence of H2O2. The peroxidase-like behaviors of this material are consistent with the Michaelis-Menten equation. An electrochemical sensor based on this material exhibits a wide working range (0.2 μM–0.745 mM and 0.745–5.345 mM), a low detection limit of 67 nM, and promising sensitivity of 158.16 μA·mM−1cm−2 for H2O2 in 0.1 M phosphate buffered (PB) solution. In addition, the H2O2 released from human liver cancer (HepG2) cells is successfully detected by the sensor, proving its potential application in situ H2O2 detection.

Design, Synthesis, Molecular docking, and biological evaluation of novel 2,3-diaryl-1,3-thiazolidine-4-one derivatives as potential anti-inflammatory and cytotoxic agents

A new series of 2,3-diaryl-1,3thiazolidin-4-one derivatives was designed, synthesized, and evaluated for their cytotoxicity and COXs inhibitory activities. Among these derivatives, compounds 4 k and 4j exhibited the highest inhibitory activities against COX-2 at IC50 values of 0.05 and 0.06 μM, respectively. Compounds 4a, 4b, 4e, 4 g, 4j, 4 k, 5b, and 6b, which exhibited the highest inhibition% against COX-2, were evaluated for their anti-inflammatory activity in rats. Results showed 41.08–82.00 % inhibition of paw edema thickness by the test compounds compared to celecoxib (inhibition% = 89.51 %). In addition, compounds 4b, 4j, 4 k, and 6b exhibited better GIT safety profiles compared to celecoxib and indomethacin. The four compounds were also evaluated for their antioxidant activity. The results revealed the highest antioxidant activity for 4j (IC50 = 45.27 μM) comparable to torolox (IC50 = 62.03 μM). The antiproliferative activity of the new compounds was evaluated against HePG-2, HCT-116, MCF-7, and PC-3 cancer cell lines. The results showed the highest cytotoxicity for compounds 4b, 4j, 4 k, and 6b (IC50 = 2.31–27.19 μM), with 4j being the most potent. Mechanistic studies revealed the ability of 4j and 4 k by inducing marked apoptosis and cell cycle arrest at the G1 phase in HePG-2 cancer cells. These biological results may also suggest a role for COX-2 inhibition in the antiproliferative activity of these compounds. The results of the molecular docking study for 4 k and 4j into the active site of COX-2 revealed good fitting and correlation with the results of the in vitro COX‑2 inhibition assay.

The anticancer, anti-oxidant, and antibacterial activities of chitosan-lecithin-coated parthenolide/tyrosol hybrid nanoparticles

Tyrosol (TYR) and parthenolide (PLT) have been used as synthetic antioxidant and natural anticancer compounds. In the current study, we aimed to synthesize an encapsulated complex of both PLT and TYR in a hybrid coating layer consisting of lecithin and chitosan molecules, a proper biocompatible drug delivery system to evaluate its antibacterial and anticancer potentials on human liver HepG2 and pancreatic Panc cancer cell lines. The chitosan-lecithin-coated PLT/TYR nanoparticles (clPT-NPs) were synthesized applying an auto-self-assembling method. The clPT-NPs were characterized utilizing DLS, FTIR, zeta potential, and TEM analysis. The clPT-NPs’ antioxidant activity was measured by running ABTS and DPPH antioxidant assays. Moreover, the antibacterial potential of clPT-NPs was evaluated by applying disk diffusion, MIC, and MBC assays. Finally, the nanoparticles’ cytotoxicity and apoptotic activity were studied by conducting MTT, Flow cytometry, AO/PI cell staining, and real-time PCR techniques. The clPT-NPs (38 nm) exhibited significant antioxidant activity by inhibiting ABTS and DPPH radicals at 187 and 290 μg/mL IC50 concentrations, respectively. Also, the nanoparticles induced a notable antibacterial activity against Staphylococcus aureus at 0.0625 mg/mL MIC and 0.125 mg/mL MBC concentrations. The clPT-NPs selectively decreased the cancer cells’ survival and increased the apoptotic dead cells by up-regulating apoptotic gene expression (BAX and Cas-8) and down-regulating BCL-2 anti-apoptotic gene expression. The PLT toxicity has been merged with improved TYR antioxidant activity, which has been functionalized in a safe, biocompatible hybrid nano-delivery system.

Preliminary Structural Characterization of Selenium Nanoparticle Composites Modified by Astragalus Polysaccharide and the Cytotoxicity Mechanism on Liver Cancer Cells.

Astragalus alcohol soluble polysaccharide (AASP) could present superior water solubility and antitumor activity with high concentration. Selenium nanoparticles (SeNPs) have received growing attention in various fields, but their unstable property increases the application difficulties. In the present study, functionalized nano-composites (AASP-SeNPs) were synthesized through SeNPs using AASP (average molecular weight of 2.1 × 103 Da) as a surface modifier, and the preliminary structural characteristics and inhibitory mechanism on liver cancer (HepG2) cells were investigated. Results showed that AASP-SeNPs prepared under a sodium selenite/AASP mass ratio of 1/20 (w/w) were uniformly spherical with a mean grain size of 49.80 nm and exhibited superior dispersivity and stability in water solution. Moreover, the composites could dose-dependently inhibit HepG2 cell proliferation and induce apoptosis through effectively regulating mitochondria-relevant indicators including ΔΨm depletion stimulation, intracellular ROS accumulation, Bax/Bcl-2 ratio improvement, and Cytochrome c liberation promotion. These results provide scientific references for future applications in functional food and drug industries.

BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies.

In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds BF1-9. These bromobenzofuran-oxadiazole structural hybrids BF1-9 were evaluated in vitro against anti-hepatocellular cancer (HepG2) cell line as well as for their in silico therapeutic potential against six key cancer targets, such as EGFR, PI3K, mTOR, GSK-3β, AKT, and Tubulin polymerization enzymes. Bromobenzofuran structural motifs BF-2, BF-5, and BF-6 displayed the best anti-cancer potential and with the least cell viabilities (12.72 ± 2.23%, 10.41 ± 0.66%, and 13.08 ± 1.08%), respectively, against HepG2 liver cancer cell line, and they also showed excellent molecular docking scores against EGFR, PI3K, mTOR, and Tubulin polymerization enzymes, which are major cancer targets. Bromobenzofuran-oxadiazoles BF-2, BF-5, and BF-6 displayed excellent binding affinities with the active sites of EGFR, PI3K, mTOR, and Tubulin polymerization enzymes in the molecular docking studies as well as in MMGBSA and MM-PBSA studies. The stable bindings of these structural hybrids BF-2, BF-5, and BF-6 with the enzyme targets EGFR and PI3K were further confirmed by molecular dynamic simulations. These investigations revealed that 2,5-dimethoxy-based bromobenzofuran-oxadiazole BF-5 (10.41 ± 0.66% cell viability) exhibited excellent cytotoxic therapeutic efficacy. Moreover, computational studies also suggested that the EGFR, PI3K, mTOR, and Tubulin polymerization enzymes were the probable targets of this BF-5 scaffold. In silico approaches, such as molecular docking, molecular dynamics simulations, and DFT studies, displayed excellent association with the experimental biological data of bromobenzofuran-oxadiazoles BF1-9. Thus, in silico and in vitro results anticipate that the synthesized bromobenzofuran-oxadiazole hybrid BF-5 possesses prominent anti-liver cancer inhibitory effects and can be used as lead for further investigation for anti-HepG2 liver cancer therapy.

In Vitro Anticancer Activity of Hexane and Ethyl acetate Extracts of Leaf, Petiole and Rhizome of Petasites japonicus

The aim of this study was to ascertain the effect of different solvents on extraction yield, antioxidant activity and cytotoxicity of extracts from Petasites japonicus (Siebold & Zucc.) Maxim. P. japonicus, widely distributed in Korea, Japan and China, is used as a culinary vegetable and a traditional medicine for asthma, migraines and tension headaches, and allergic rhinitis. In this study, twelve extracts from leaves, petioles and rhizomes of P. japonicus were evaluated for their antiproliferative activity against AGS, HepG2, HCT-116, and MCF-7 cancer cell lines. Plant extracts were fractionated using hexane, EtOAc, BuOH and distilled water, after which the antiproliferative activity was measured by MTT assay. Cell viability decreased in a dose dependent manner in response to the hexane and ethyl acetate extracts for all cell lines, with a significant decrease in cell viability being observed for 100 μg/ml and 75 μg/ml in the AGS and HepG2 cancer cell lines (p < 0.05). The leaf extract appeared to be more potent against HepG2, as indicated by IC50 values of 4.31 μg/ml for approximately 2.5- and 6.3-fold compared with rhizome and petiole extracts, respectively. The IC50 values of hexane extracts from leaves and rhizomes against AGS, HepG2, and MCF-7 human cell lines were greater than those of other extracts, while ethyl acetate extracts from petioles showed higher significant effect for all cell lines. Hexane and EtOAc extracts exerted their antiproliferative activity in four cancer cell lines. Overall, the results indicate that P. japonicus has the potential to be developed into selective anticancer nutraceutical and/or pharmaceutical treatments with low cost.

Small molecules targeting the NADH-binding pocket of VDAC enhance T cell cytotoxicity and selectively inhibit cancer cell proliferation.

Adoptive cell therapy involves administration of cytotoxic immune cells. Upon activation of naïve T cells, CD8+ (cytotoxic) T cells increase both mitochondrial metabolism and glycolysis. Upregulated mitochondrial metabolism is essential for the activation of effector T cells. Voltage dependent anion channels (VDAC 1/2/3) regulate the flux of most metabolites entering and exiting mitochondria. VDAC opening increases mitochondrial metabolism. NADH binding to a VDAC pocket, conserved in all isoforms, closes the channel. The small molecules SC01 and SC18 bind to the VDAC-NADH binding pocket. We hypothesize that SC01 and SC18 stabilize VDAC in an open state enhancing T cell oxidative metabolism, survival and cytotoxicity. We used melanoma epitope gp100 reactive mouse splenic CD8+ T cells, HepG2 and SNU-449 human hepatocarcinoma cancer cells, and B16 mouse melanoma cells. We determined T cell activation (CD25 expression), proliferation (Ki67), cytokine secretion (IFNγ, TNFα), cytolytic activity (granzyme-B), and expression of memory markers CD44 and CD62L, by FACS. We assessed mitochondrial membrane potential (ΔΨm) and NADH by confocal microscopy. Cell proliferation and cell death were determined by cell count and propidium iodide uptake, respectively. VDAC isoform distribution in T cells was ∼54%, 24% and 22% for VDAC 1, 2 and 3, respectively. SC18 moderately decreased T cell ΔΨm and NADH. SC01 and SC18 did not affect proliferation or activation of splenic CD8+ T cells exposed to cognate antigen (gp100). By contrast, SC18 inhibited cell proliferation in SNU-449, HepG2, and B16 cells. SC18 also increased the secretion of IFNγ, TNF-α, and granzyme-B. Memory markers determined by CD44 and CD62L co-expression were unchanged. These data suggest a two-sided antitumor property of SC18, that enhances T cell cytotoxicity and selectively inhibits cancer cell proliferation.

Cannabinol inhibits cell growth and triggers cell cycle arrest and apoptosis in cancer cells

Cannabinol (CBN) is a weak-psychoactive cannabinoid and has been shown to exert several bio-logical activities. At the same time, not much is known about the anti-cancer activities of CBN. In this report, we characterized the anti-tumor effects of CBN on the glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines. We found that CBN reduces the proliferation of the analyzed cancer cells and modulates the level of cannabinoid receptors, including GPR18, CB2 and GPR55. Furthermore, CBN inhibits the ERK1/2 pathway in A172 and HepG2 cells, while suppressing the AKT pathway in HCC1086 cells. Moreover, CBN may cause apoptosis through downregulation of p21 and p27 as well as a cell cycle arrest at G1 or S-phase via decreasing the CDK1, CDK2, and cyclin E1 levels. Taken together, these results offer new insights into the anti-cancer properties of CBN.

Synthesis, molecular docking study and anticancer activity of novel 1,3,4-oxadiazole derivatives as potential tubulin inhibitors

The current study reports on the synthesis and anticancer efficacy of novel oxadiazole derivatives (8a-f) as tubulin polymerization inhibitors. NMR, mass, and elemental studies were used to confirm the newly produced compounds. In contrast to the conventional medicine colchicine, compounds 8e and 8f demonstrated stronger sensitivity and improved IC50 values in the range of 3.19–8.21 μM against breast MCF-7, colorectal HCT116, and liver HepG2 cancer cell lines. The target compounds were tested for enzymatic activity against the tubulin enzyme. Compounds 8e and 8f were shown to have the most effective inhibitory action among the new compounds, with IC50 values of 7.95 and 9.81 nM, respectively. As compared to the reference drug, molecular docking investigations of the developed compounds revealed the crucial hydrogen bonding in addition to the hydrophobic interaction at the binding site, assisting in the prediction of the structural requirements for the found anticancer activity. These findings indicate that the 1,3,4-oxadizole scaffold has the potential for future research into new anticancer medicines.

Evaluation of Ruthenium(II) N-Heterocyclic Carbene Complexes as Enzymatic Inhibitory Agents with Antioxidant, Antimicrobial, Antiparasitical and Antiproliferative Activity.

A series of [RuCl2(p-cymene)(NHC)] complexes were obtained by reacting [RuCl2(p-cymene)]2 with in situ generated Ag-N-heterocyclic carbene (NHC) complexes. The structure of the obtained complexes was determined by the appropriate spectroscopy and elemental analysis. In addition, we evaluated the biological activities of these compounds as antienzymatic, antioxidant, antibacterial, anticancer, and antiparasitic agents. The results revealed that complexes 3b and 3d were the most potent inhibitors against AchE with IC50 values of 2.52 and 5.06 μM mL-1. Additionally, 3d proved very good antimicrobial activity against all examined microorganisms with IZ (inhibition zone) over 25 mm and MIC (minimum inhibitory concentration) < 4 µM. Additionally, the ligand 2a and its corresponding ruthenium (II) complex 3a had good cytotoxic activity against both cancer cells HCT-116 and HepG-2, with IC50 values of (7.76 and 11.76) and (4.12 and 9.21) μM mL-1, respectively. Evaluation of the antiparasitic activity of these complexes against Leishmania major promastigotes and Toxoplasma gondii showed that ruthenium complexes were more potent than the free ligand, with an IC50 values less than 1.5 μM mL-1. However, 3d was found the best one with SI (selectivity index) values greater than 5 so it seems to be the best candidate for antileishmanial drug discovery program, and much future research are recommended for mode of action and in vivo evaluation. In general, Ru-NHC complexes are the most effective against L. major promastigotes.

Apoptotic effects of phenols from the twigs and leaves of Garcinia nujiangensis

In order to find potential agents for treating cancer disease in naturally occurring compounds, we conducted a systematic phytochemical investigation on the endemic species of Garcinia nujiangensis. Three new biphenyl derivatives (1–3) and one new polycyclic polyprenylated benzophenone (4), together with four known benzophenone analogues (5–8), have been isolated from the CH2Cl2 extract of the twigs and leaves of G. nujiangensis. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known analogues. Experimental and calculated ECD method was used to determine the absolute configuration of 1 and 4. Moreover, compounds 5–7 were isolated for the first time from this species. The cytotoxicities of the new compounds were evaluated using HL-60, HepG2, and A549 human cancer cell lines. Compound 4 showed more significant antiproliferative effects against HepG2 cells with an IC50 value of 11.38 ± 0.79 μM than that of three biphenyl derivatives. The morphological features of apoptosis were evaluated in 4-treated HepG2 cells. Compound 4 effectively prevented the cell cycle progression of HepG2 cells in G2 phase. Additionally, western blot analysis indicated that treatment of 4 on HepG2 cells led to decreased expression of anti-apoptotic Bcl-2 and pro-Caspase-3, and increased protein expression of both pro-apoptotic Bax and cleaved PARP with reference to β-actin. Overall, our results suggested that the active polycyclic polyprenylated benzophenone derivatives in the twigs and leaves of G. nujiangensis can be used as a valuable source of bioactive compounds for the pharmaceutical industry.

Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV–vis spectroscopy, and thermal denaturation. Results showed that conjugates 34–37 interacted very strongly with ct-DNA (ΔT m = 10.00–13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro. The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe2+ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells.

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies.

Fifteen quinazoline derivatives were designed and synthesized as DNA intercalators. The cytotoxicity of the designed members was assessed against HCT-116 and HepG2 cancer cell lines. In addition, the topoisomerase II (Topo II) inhibitory effect was assessed. Compound 16 was the most cytotoxic and Topo II inhibitor with low cytotoxicity against Vero cells. Compounds 16, 17, and 18 showed significant DNA binding affinities. Compound 16 showed Topo II catalytic inhibitory effect at a concentration of 10 μM. Further mechanistic investigations revealed the capability of compound 16 to induce apoptosis in HCT-116 cells and arrest the growth at the S and G2/M phases. Also, compound 16 showed a significant increase in the level of BAX (2.18-fold) and a marked decrease in the level of Bcl-2 (1.9-fold) compared to the control cells. In silico studies revealed the ability of the synthesized members to bind to the DNA-Topo II complex.

Bacteriocin-Nanoconjugates (Bac10307-AgNPs) Biosynthesized from Lactobacillus acidophilus-Derived Bacteriocins Exhibit Enhanced and Promising Biological Activities.

The proteinaceous compounds produced by lactic acid bacteria are called bacteriocins and have a wide variety of bioactive properties. However, bacteriocin's commercial availability is limited due to short stability periods and low yields. Therefore, the objective of this study was to synthesize bacteriocin-derived silver nanoparticles (Bac10307-AgNPs) extracted from Lactobacillus acidophilus (L. acidophilus), which may have the potential to increase the bioactivity of bacteriocins and overcome the hurdles. It was found that extracted and purified Bac10307 had a broad range of stability for both temperature (20-100 °C) and pH (3-12). Further, based on Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis, its molecular weight was estimated to be 4.2 kDa. The synthesized Bac10307-AgNPs showed a peak of surface plasmon resonance at 430 nm λmax. Fourier transform infrared (FTIR) confirmed the presence of biological moieties, and transmission electron microscopy (TEM) coupled with Energy dispersive X-Ray (EDX) confirmed that AgNPs were spherical and irregularly shaped, with a size range of 9-20 nm. As a result, the Bac10307-AgNPs displayed very strong antibacterial activity with MIC values as low as 8 μg/mL for Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), when compared to Bac10307 alone. In addition, Bac10307-AgNPs demonstrated promising in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 116.04 μg/mL) and in vitro cytotoxicity against human liver cancer cells (HepG2) (IC50 = 135.63 μg/mL), more than Bac10307 alone (IC50 = 139.82 μg/mL against DPPH and 158.20 μg/mL against HepG2). Furthermore, a protein-protein molecular docking simulation study of bacteriocins with target proteins of different biological functions was also carried out in order to ascertain the interactions between bacteriocins and target proteins.

New benzothiazole hybrids as potential VEGFR-2 inhibitors: design, synthesis, anticancer evaluation, and in silico study

A new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione 4a–e, 1,3,4-thiadiazole aryl urea 6a–d, and cyanothiouracil moieties 8a–d was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, 4a was the most potent showing IC50 of 5.61, 7.92, and 3.84 µM, respectively. Furthermore, compounds 4e and 8a proved to have strong impact on breast cancer cell line with IC50 of 6.11 and 10.86 µM, respectively. The three compounds showed a good safety profile towards normal WI-38 cells. Flow cytometric analysis of the three compounds in MCF-7 cells revealed that compounds 4a and 4c inhibited cell population in the S phase, whereas 8a inhibited the population in the G1/S phase. The most promising compounds were subjected to a VEGFR-2 inhibitory assay where 4a emerged as the best active inhibitor of VEGFR-2 with IC50 91 nM, compared to 53 nM for SOR. In silico analysis showed that the three new hybrids succeeded to link to the active site like the co-crystallized inhibitor SOR.

Biosynthesized Zinc Oxide Nanoparticles Using Ziziphus Jujube Plant Extract Assisted by Ultrasonic Irradiation and Their Biological Applications

The green biosynthesis of zinc oxide nanoparticles (GBS ZnO NPs) using Ziziphus jujuba leaves extract assisted by ultrasonic irradiation was reported in this research work. The green biosynthesized ZnO NPs were characterized using different techniques and the results revealed the synthesis of hexagonal wurtzite crystal of GBS ZnO nanoparticles; per the XRD measurement, with average practice size of 90 ± 10 nm; based on both SEM and TEM images, and with specific surface area of 14.23 m2/g; per the nitrogen gas adsorption/desorption isotherms. The antibacterial activity of the prepared GBS ZnO NPs was explored against S. aureus and E. coli bacteria using different evaluation methods; disc diffusion, column (filter), and aqueous solution, and the results showed the effective antibacterial activities against S. aureus and E. coli bacteria, as the inhibition zones were 15 mm and 11 mm for the E. coli and S. aureus, respectively. Moreover, the anticancer activity of the green biosynthesized ZnO NPs was evaluated on two different cancer cells; human colon cancer cell lines (HCT-116) and the human liver cancer (HepG2) cells, and the experiments showed that GBS ZnO NPs had an outstanding cytotoxic effect on both cancer cell lines, as well as dose-dependent behavior, as the viability of the cancer cells decreased by using GBS ZnO NPs at concentrations of 10 and 20 µg/mL. Cell lines (HCT-116) and the human liver cancer (HepG2) cells, and the experiments showed that GBS ZnO NPs had an outstanding cytotoxic effect on both cancer cell lines, as the GBS ZnO NPs enhanced the cytotoxicity mechanism by generating ROS as the nanoparticles interact with cells, lower its cellular defense mechanism, and accordingly cause apoptosis to the cell.