Cell Line HepG2 Research Articles

Cytotoxic and antimicrobial metabolites from the marine-derived fungus Aspergillus sp. OPR23-FS01

Chemical investigation of a marine-derived fungus Aspergillus sp. OPR23-FS01 resulted in the isolation of a new unsaturated fatty acid featuring a terminal olefin, 10-methoxy-2-methylene-10-oxodecanoic acid (1), two new natural compounds, 2-carboxy-2′-methyl-azobenzene (2) and 1,3,9-trimethyluric acid (3), and 11 previously described metabolites, pantheric acid C (4), pantheric acid D (5), 2-furoic acid (6), 5-(hydroxymethyl)-2-furancarboxylic acid (7), sporogen-AO 1 (8), gliocladic acid (9), hydroheptelidic acid (10), ditryptophenaline (11), emodin (12), uridine (13), and thymidine (14). Their structures were identified by comprehensive analyses of the spectroscopic methods, including NMR and HRESI mass spectra. Compound 2 possesses a rare diazenyl group among the previously reported fungal metabolites. Compound 8 showed significant cytotoxicity against both HepG2 and MCF-7 cell lines in a dose-dependent manner, with IC50 values of 4.66 ± 0.24 and 5.54 ± 0.28 μM, respectively. Compounds 1−5 and 8−11 displayed antimicrobial effect against Enterococcus faecalis ATCC299212, with MIC values ranging from 32 to 128 μM, whereas 1, 4, 5, and 8−11 inhibited Candida albicans ATCC10231 growth, with MIC values in a range of 32−256 μM.

Seven glycosides from the roots of Scrophularia ningpoensis

Three new glycosides (1–3) together with four known ones (4–7) were isolated from the roots of Scrophularia ningpoensis. Their structures were elucidated through extensive analysis of HR-ESI-MS, NMR, and ECD spectra. The anti-inflammatory potential of the new compounds was evaluated by measuring their ability to inhibit lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 macrophage cells. In addition, the cytotoxic effects of the new compounds on HepG2, 4T1, and A549 cell lines were evaluated.

Propolis Nanoparticles Combined with Gamma-Irradiation Enhance the Potency of Anticancer Against HepG2 Cell Lines: Invitro Investigation

Propolis Nanoparticles Combined with Gamma-Irradiation Enhance the Potency of Anticancer Against HepG2 Cell Lines: Invitro Investigation

Nutritional values, antioxidant, and cytotoxic activities of selected edible marine macroalgae: a comparative study

AbstractThe objective of this study is to assess the chemical composition, nutritional values, and bioactivities of four macroalgae from the Egyptian Red Sea coasts using standard methods. Of these, three Rhodophyceae species, Digenea simplex (D. simplex), Laurencia papillosa (L. papillosa), and Galaxaura oblongata (G. oblongata), and one Phyaeophyceae species, Turbinaria decurrens (T. decurrens), were selected. The results of proximate and chemical composition analyses based on the algal dry weight (DW) showed that carbohydrate content was the highest, ranging from 32.47 ± 1.03% to 45.5 ± 1.23%. Other algal constituents, including ash, protein, moisture, sulfate, lipid, phenolics, and flavonoids, have contents that depend on the algal species. Besides, HPLC analysis revealed that each algal extract contained varying amounts of nine phenolic acids. Atomic absorption spectrometry, the HPLC-Pico-Tag method, the ion chromatography technique, and GC/MS analyses were used to determine the chemical profiles of the elemental, amino acid, halide, and fatty acid of each algal extract. Bioactivities revealed that both the •DPPH and ABTS assays showed that all the algae studied had a significant ability to scavenge free radicals in a dosage-dependent way. They also had strong selective cytotoxic activity against HEPG-2 and HCT-116 cell lines, but only weak activity against MCF-7 and A549 cell lines. Finally, our findings suggested that the selected algae might be efficiently used as nutraceuticals and functional foods, indicating an increase in their proliferation.

Targeted delivery of interleukin-12 plasmid into HepG2 cells through folic acid conjugated graphene oxide nanocarrier.

Successful gene therapy relies on carriers to transfer genetic materials with high efficiency and low toxicity in a targeted manner. To enhance targeted cell binding and uptake, we developed and synthesized a new gene delivery vector based on graphene oxide (GO) modified by branched polyethyleneimine (BPEI) and folic acid (FA). The GO-PEI-FA nanocarriers exhibit lower toxicity compared to unmodified PEI, as well as having the potential to efficiently condense and protect pDNA. Interestingly, increasing the polymer content in the polyplex formulation improved plasmid transfer ability. Substituting graphene oxide for PEI at an N/P ratio of 10 in the HepG2 and THP1 cell lines improved hIL-12 expression by up to approximately eightfold compared to simple PEI, which is twice as high as GO-PEI-FA in Hek293 at the same N/P ratio. Therefore, the GO-PEI-FA described in this study may serve as a targeting nanocarrier for the delivery of the hIL-12 plasmid into cells overexpressing folic acid receptors, such as those found in hepatocellular carcinoma.

Integrated in silico and in vitro discovery of a new anticancer thiadiazole analog targeting VEGFR-2

In this work, a new thiadiazole analogue (TDA) was designed with the intention of incorporating key features of Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) inhibitors, and then was examined computationally and experimentally. In vitro (cytotoxicity on MCF-7, HepG2 and WI-38 cell lines, in vitro VEGFR-2 assay, cell cycle analysis, apoptosis assays, RT-PCR, and migration studies), in addition to in silico (molecular docking, ADMET, MD simulations and DFT studies) were conducted. Prior to synthesis, docking and ADMET studies yielded predictions indicating favorable activity and drug likeness. After synthesis, the results demonstrated promising inhibitory activity of TDA on MCF-7 and HepG2 cancer cell lines. These results were notably close to those of sorafenib. The in vitro VEGFR-2 assay revealed significant inhibition, with an IC50 value of 0.283 µM. Selectivity studies indicated a favorable safety profile, with reduced toxicity towards normal lung cells (WI-38). Cell cycle analysis of TDA revealed a significant arrest in the G0-G1 phase, compared to the control group. Apoptosis assays demonstrated a considerable increase in programmed cell death, particularly in the early stages as opposed to the control group. Additionally, there was a notable increase in the expression of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl2 in MCF-7 cells treated with TDA. TDA also exhibited an anti-angiogenic potential through decreasing the abilities of the MCF-7 cells to migrate and heal. Computationally, various MD simulations studies indicated stable interactions between TDA and VEGFR-2 over 200 ns on both mechanical and energetic levels. DFT studies confirmed reactivity and stability of TDA. These comprehensive findings emphasize TDA’s potential as a multi-targeted candidate for further development in cancer therapy. The promising inhibitory activity, favorable safety profile, and mechanistic insights highlight TDA as a noteworthy contender through further in vivo studies and modifications.

Novel role of MHC class II transactivator in hepatitis B virus replication and viral counteraction.

The major histocompatibility class II (MHC II) transactivator, known as CIITA, is induced by Interferon gamma (IFN-γ) and plays a well-established role in regulating the expression of class II MHC molecules in antigen-presenting cells. Primary human hepatocytes (PHH) were isolated via therapeutic hepatectomy from two donors who tested negative for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV). The hepatocellular carcinoma (HCC) cell lines HepG2 and Huh7 were used for the mechanistic study, and HBV infection was performed in HepG2-NTCP cells. HBV DNA replication intermediates and secreted antigen levels were measured using Southern blotting and ELISA, respectively. We identified a non-canonical function of CIITA in the inhibition of hepatitis B virus (HBV) replication in both HCC cells and patient-derived PHH. Notably, in vivo experiments demonstrated that HBV DNA and secreted antigen levels were significantly decreased in mice injected with the CIITA construct. Mechanistically, CIITA inhibited HBV transcription and replication by suppressing the activity of HBV-specific enhancers/promoters. Indeed, CIITA exerts antiviral activity in hepatocytes through ERK1/2-mediated down-regulation of the expression of hepatocyte nuclear factor 1α (HNF1α) and HNF4α, which are essential factors for virus replication. In addition, silencing of CIITA significantly abolished the IFN-γ-mediated anti-HBV activity, suggesting that CIITA mediates the anti-HBV activity of IFN-γ to some extent. HBV X protein (HBx) counteracts the antiviral activity of CIITA via direct binding and impairing its function. Our findings reveal a novel antiviral mechanism of CIITA that involves the modulation of the ERK pathway to restrict HBV transcription. Additionally, our results suggest the possibility of a new immune avoidance mechanism involving HBx.

CYTOTOXIC ACTIVITY OF FRACTIONS AND COMPOUNDS FROM PEPEROMIA PELLUCIDA

Peperomia pellucida is a widely distributed herb and commonly used in folk medicine for the treatment of various disorders. The present study reported the isolation, elucidation of compounds from the whole plant and their cytotoxic activities on Hep G2 (HB - 8065TM, hepatocellular carcinoma), A549 (CCL-185™, pulmonary adenocarcinoma), and MCF-7 (HTB - 22TM, breast cancer) cell lines. As a result, velutin exhibited the most significant cytotoxicity against Hep G2, A549, and MCF-7 cell lines with IC50 values of 34.00, 30.85, and 41.33 μg/mL, respectively.

Discovery of new eremophilanes from the marine-derived fungus Emericellopsis maritima BC17 by culture conditions changes: evaluation of cytotoxic and antimicrobial activities

In our previous studies, the marine-derived fungus Emericellopsis maritima BC17 was found to produce new eremophilane-type sesquiterpenoids on solid media. In order to explore its potential to produce more metabolites, E. maritima BC17 was subjected to a one strain-many compounds (OSMAC) analysis leading to the discovery of three new eremophilanes (1-3) and fourteen known derivatives (4-17) in the liquid media Czapek Dox and PDB. Their structures were established by extensive analyses of the 1D and 2D NMR, and HRESIMS data, as well as ECD data for the assignment of their absolute configurations. Antitumoral and antimicrobial activities of the isolated metabolites 1, 3, 11, and 15 were investigated. PR toxin 3-deacetyl (15) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058 and Mia PaCa-2 human cancer cell lines with IC50 values ranging from 2.5 to 14.7 µM. In addition, 15 exhibited selective activity against methicillin-sensitive Staphylococcus aureus ATCC29213 at the highest concentration tested of 128 µg/mL.

Ultrasound-assisted synthesis of novel Schiff bases from 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde and their cytotoxicity, apoptosis, cell cycle, molecular docking, and ADMET profiling

With the ultimate goal of discovering new anticancer agents, this study involved the design and synthesis of fifteen novel Schiff bases 4a,b, 5, 6a–d, 7a–e, and 8–10 which contain 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole moiety. The synthetic method depended on reaction of 3-(2-oxo-2H-chromen-3-yl)-1-(4-phenylthiazol-2-yl)-1H-pyrazole-4-carboxaldehyde (3) with a series of aromatic and heteroaryl amines under ultrasound irradiation to explore the influence of aromatic and heteroaryl rings on biological activity. The chemical structures of these Schiff bases were fully elucidated using various spectral and elemental analyses. The antiproliferative activities of the Schiff bases were studied by the standard SRB method. Among the new 15 Schiff bases, derivatives 4a,b, 5, and 7b have significant cytotoxic effects against PC3, HepG2, and HCT116 cancer cell lines. These four bioactive Schiff bases significantly increased the late apoptosis of all studied tumor cells. Also, both products 4a and 4b arrested the cell cycle at the G1 phase, while both compounds 5 and 7b arrested the S and G2 phases against PC3 cells. In addition, the products 4a, 4b, 5, and 7b have promising high abilities to arrest the cell cycle at the G2 phase against HepG2 and HCT116 cells. The different substitutions on the aryl ring were the basis for the structure–activity relationship study. The molecular docking study confirmed good binding interactions of these compounds with Cyclin-dependent kinase 8 (CDK-8) receptor, while the absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction supported that these bioactive products can be promising anticancer agents.

The Search for and Functional Analysis of Genetic Variants in microRNA-Binding Sites using Massively Parallel Reporter Assay.

A large-scale search for the genetic variants with a bias in the representation of alleles in transcriptome data (AE SNPs) and the binding sites in microRNA 3'-UTRs was performed and their functional significance was assessed using massively parallel reporter assay (MPRA). Of the 629,559 associated "SNP-gene" pairs (eQTLs) discovered in the human liver tissue according to the GTEx Analysis V8 data, 4394 polymorphic positions in the 3'-UTRs of the genes, which represent the eQTLs for these genes were selected. The TargetScanHuman 7.0 algorithm and PolymiRTS database were searched for the potential microRNA-binding sites. Of the predicted microRNA sites affected by eQTL-SNPs, we selected 51 sites with the best evidence of functionality according to Ago2-CLIP-seq, CLEAR-CLIP, and eCLIP-seq for RNA-binding proteins. For MPRA, a library of the plasmids carrying the main and alternative alleles for each AE SNP (in total, 102 constructs) was created. Allele-specific expression for 6 SNPs was detected by transfection of the HepG2 cell line with the constructed plasmid library and sequencing of target DNA and RNA sequences using the Illumina (MiSeq) platform.

Assessing the antimicrobial and cytotoxic activities of VO(IV), Cr(III), Cu(II)-metformin-schiff-base's complexes enhanced by gold nanoparticles

A new series of VO(IV), Cr(III), and Cu(II) complexes have been synthesized by condensation of metformin with β-diketones (acetylacetone, benzoylacetone, dibenzoylmethane) in the presence of metal salts. The elemental analysis, magnetic susceptibility, conductivity assessments, Infra-Red, UV–visible spectroscopy measurements, SEM, XRD, ESR, GCMS–, DTA, and DTG were used to characterize the novel compounds. The results show that every complex has a metal: ligand ratio of 1:1. The complexes exhibit distorted tetrahedral structural geometry for Cu(II), square pyramidal and octahedral geometry for VO(IV), and octahedral geometry for Cr(III), according to their electronic absorption spectra and magnetic susceptibility studies. Using the computer program Expo2014, crystallographic parameters were estimated for the complexes. The outcomes show that every complex has triclinic crystal structures with the space group P-1, apart from complex [VOL1OSO3], which has a monoclinic structure with the P 1 2 1 space group. In contrast to the complex [VOL1OSO3], which includes monodentate sulfate, conductivity data, XRD, EDX, and GC–MS verified the purity and composition of the compounds being studied. IR data showed that the complexes Na.[VOL2O2SO2] and Na.[VOL3O2SO2] has bidentate chelating sulfate ion. TG, DTG, and DTA have all been used to investigate the complexes' thermal stabilities. Some Schiff-base metformin complexes under investigation had their biological activity evaluated both with and without the addition of AuNPs. Various bacteria and harmful fungi strains have been used to screen the antimicrobial activity. The findings indicate that only copper-loaded Schiff base complexes on AuNPs gave promising results versus Staphylococcus aureus, Escherichia coli, Salmonella, and Candida albicans. On human cell lines of breast cancer (MCF7) and cancer of the human liver (HEPG2), in vitro cytotoxic activity was tested. Results showed that vanadium benzoylacetone doped with gold nanoparticles, with an IC50 value of 7 µg/ml against the HEPG2 cell line and 9.8 against MCF7 has the most effective cytotoxic effect.

A ‘molecular chameleon’ mimic ZrIV-consolidated Fluoro-specific coordination complex and arseno-selective supramolecular metallogelator as a phase discriminatory sensing probe: Substantiation of in-vitro and in-silico approaches with the sensing response

ZrIV consolidated solvatochromic and halochromic coordination complex [ZrIV-ABH (C)] has been synthesized which exhibited promising selectivity and sensitivity towards aqueous phase F-. Upon addition of a trace amount of F-, ZrIV-ABH (C) showcased concentration-reliant chromogenic alteration and fluorogenic spectral shift. Sensing phenomena were corroborated through, UV–Vis spectroscopy, photoluminescence and cyclic voltammetry along with an in-silico approach. The equivalence-dependent chromo-fluorogenic alteration upon the addition of F- on ZrIV-ABH (C), further has been validated theoretically by means of diminution of energy of fluoro-adducts. The bio-compatibility of the probe has been validated through in-vitro detection of F- from hepatocytes of zebrafish and HepG2 cell line. The anti-interfering sensing response of F- among its geogenic lethal congeners has been further utilized to formulate a six-input-two-output logic gate circuitry. Furthermore, ZrIV epicentric coordination complex-based metallogelator probe namely, ZrIV-ABH (G) has been synthesized which can detect AsO2- selectively from the aqueous phase. ZrIV-ABH (G) has been utilized for the real-field validation of aquifer-genic AsO2-. The solvent as well as the temperature-specific formation of ZrIV-ABH (G) metallogelator has been substantiated by rheological behavior. The thermosensitive activity of ZrIV-ABH (G) has been professed by means of chromogenic alteration and fluorogenic turn-on response at a particular elevated temperature. Therefore, this phase-selective switching of sensing response from F- to AsO2- validated its endurance as a value-added contender in its category.

Hindering the biofilm of microbial pathogens and cancer cell lines development using silver nanoparticles synthesized by epidermal mucus proteins from Clarias gariepinus

Scientists know very little about the mechanisms underlying fish skin mucus, despite the fact that it is a component of the immune system. Fish skin mucus is an important component of defence against invasive infections. Recently, Fish skin and its mucus are gaining interest among immunologists. Characterization was done on the obtained silver nanoparticles Ag combined with Clarias gariepinus catfish epidermal mucus proteins (EMP-Ag-NPs) through UV–vis, FTIR, XRD, TEM, and SEM. Ag-NPs ranged in size from 4 to 20 nm, spherical in form and the angles were 38.10°, 44.20°, 64.40°, and 77.20°, Where wavelength change after formation of EMP-Ag-NPs as indicate of dark brown, the broad band recorded at wavelength at 391 nm. Additionally, the antimicrobial, antibiofilm and anticancer activities of EMP-Ag-NPs was assessed. The present results demonstrate high activity against unicellular fungi C. albicans, followed by E. faecalis. Antibiofilm results showed strong activity against both S. aureus and P. aeruginosa pathogens in a dose-dependent manner, without affecting planktonic cell growth. Also, cytotoxicity effect was investigated against normal cells (Vero), breast cancer cells (Mcf7) and hepatic carcinoma (HepG2) cell lines at concentrations (200–6.25 µg/mL) and current results showed highly anticancer effect of Ag-NPs at concentrations 100, 5 and 25 µg/mL exhibited rounding, shrinkage, deformation and granulation of Mcf7 and HepG2 with IC50 19.34 and 31.16 µg/mL respectively while Vero cells appeared rounded at concentration 50 µg/mL and normal shape at concentration 25, 12.5 and 6.25 µg/ml with IC50 35.85 µg/mL. This study evidence the potential efficacy of biologically generated Ag-NPs as a substitute medicinal agent against harmful microorganisms. Furthermore, it highlights their inhibitory effect on cancer cell lines.

Anticancer activity of 8-hydroxyquinoline-triphenylphosphine rhodium(III) complexes targeting mitophagy pathways

Metallodrugs exhibiting distinct mechanisms of action compared with cisplatin hold promise for overcoming cisplatin resistance and improving the efficacy of anticancer drugs. In this study, a new series of rhodium (Rh)(III) complexes containing tris(triphenylphosphine)rhodium(I) chloride [(TPP)3RhCl] (TPP = triphenylphosphine, TPP=O = triphenylphosphine oxide) and 8-hydroxyquinoline derivatives (H-XR1–H-XR4), namely [Rh(XR1)2(TPP)Cl]·(TPP=O) (Yulin Normal University-1a [YNU-1a]), [Rh(XR2)2(TPP)Cl] (YNU-1b), [Rh(XR3)2(TPP)Cl] (YNU-1c), and [Rh(XR4)2(TPP)Cl] (YNU-1d), was synthesized and characterized via X-ray diffraction, mass spectrometry and IR. The cytotoxicity of the compounds YNU-1a–YNU-1d in Hep-G2 and HCC1806 human cancer cell lines and normal HL-7702 cell line was evaluated. YNU-1c exhibited cytotoxicity and selectivity in HCC1806 cells (IC50 = 0.13 ± 0.06 μM, selectivity factor (SF) = 384.6). The compounds YNU-1b and YNU-1c, which were selected for mechanistic studies, induced the activation of apoptotic pathways and mitophagy. In addition, these compounds released cytochrome c, cleaved caspase-3/pro-caspase-3 and downregulated the levels of mitochondrial respiratory chain complexes I/IV (M1 and M4) and ATP. The compound YNU-1c, which was selected for in vivo experiments, exhibited tumor growth inhibition (58.9 %). Importantly, hematoxylin and eosin staining and TUNEL revealed that HCC1806 tumor tissues exhibited significant apoptotic characteristics. YNU-1a–YNU-1d compounds are promising drug candidates that can be used to overcome cisplatin resistance.

Carbohydrate-Functionalized Anthracene Carboximides as Multivalent Ligands and Bio-Imaging Agents.

Anthracene carboximides (ACIs) conjugated with gluco-, galacto- and mannopyranosides are synthesized, by glycosylation of N-hydroxyethylanthracene carboximide acceptor with glycosyl donors. Glycoconjugation of anthracene carboximide increases the aq. solubility by more than 3-fold. The glycoconjugates display red-shifted absorption and emission, as compared to anthracene. Large Stokes shift (λabs/ λem = 445/525 nm) and high fluorescence quantum yields (Ф) of 0.86 and 0.5 occur in THF and water, respectively. The ACI-glycosides undergo facile photodimerization in aqueous solutions, leading to the formation of the head-to-tail dimer, as a mixture of syn and anti-isomers. Solution phase and solid-state characterizations by dynamic light scattering (DLS), microscopic imaging by atomic force (AFM) and transmission electron (TEM) microscopies reveal self-assembled vesicle structures of ACI glycosides. These self-assembled structures act as multivalent glycoclusters for ligand-specific lectin binding, as evidenced by the binding of Man-ACI to Con A, by fluorescence and turbidity assays. The conjugates do not show cellular cytotoxicity (IC50) till concentrations of 50 μM with HeLa and HepG2 cell lines and are cell-permeable, showing strong fluorescence inside the cells. These properties enable the glycoconjugates to be used in cell imaging. The non-selective cellular uptake of the glycoconjugates suggests a passive diffusion through the membrane.

Design and synthesis of novel JNK inhibitors targeting liver pyruvate kinase for the treatment of non-alcoholic fatty liver disease and hepatocellular carcinoma

Non-alcoholic fatty liver disease (NAFLD) comprises a broad range of liver disease including hepatocellular carcinoma (HCC) with is no FDA-approved drug. Liver pyruvate kinase (PKL) is a major regulator of metabolic flux and ATP generation in liver presenting a potential target for the treatment of NAFLD. Based on our recent finding of JNK-5A's effectiveness in inhibiting PKLR expression through a drug repositioning pipeline, this study aims to improve its efficacy further. We synthesized a series of JNK-5A analogues with targeted modifications, guided by molecular docking studies. These compounds were evaluated for their activities on PKL expression, cell viability, triacylglyceride (TAG) levels, and the expressions of steatosis-related proteins in the human HepG2 cell line. Subsequently, the efficacy of these compounds was assessed in reducing TAG level and toxicity. Compounds 40 (SET-151) and 41 (SET-152) proved to be the most efficient in reducing TAG levels (11.51 ± 0.90 % and 10.77 ± 0.67 %) and demonstrated lower toxicity (61.60 ± 5.00 % and 43.87 ± 1.42 %) in HepG2 cells. Additionally, all synthesized compounds were evaluated for their anti-cancer properties revealing that compound 74 (SET-171) exhibited the highest toxicity in cell viability with IC50 values of 8.82 µM and 2.97 µM in HepG2 and Huh7 cell lines, respectively. To summarize, compounds 40 (SET-151) and 41 (SET-152) show potential for treating NAFLD, while compound 74 (SET-171) holds potential for HCC therapy.

Evaluation of Cytotoxicity and Apoptosis Induced by Coumarin Hydrazide-Hydrazone Derivatives in Human Hepatocellular Carcinoma Cell Line

Coumarin and aryl hydrazide-hydrazone have attracted our attention due to their vast biological properties. Previous studies suggested that coumarin-tethered aryl hydrazide-hydrazone showed potent activities against HepG2. In the present study, we investigated the cytotoxic potency of the coumarin derivatives 1 - 3 to compare with coumarin hydrazine-hydrazone hybrids 4 and 5 against hepatocellular carcinoma HepG2 and LH86 cell lines. Among the tested coumarins, hybrids 4 and 5 showed highly potent activity against HepG2 with IC50 values of 17.82 ± 2.79 and 7.87 ± 0.88 𝜇g/mL, respectively. The hybrid 4 also showed the strongest activity against LH86 cell line with IC50 values of 48.32 ± 2.64 𝜇g/mL. Further, we have studied the mechanism of action of the hybrid compounds 4 and 5 in HepG2 cells via the flow-cytometry analysis and the activation of the caspase-3 and caspase-7. The results showed that hybrids 4 and 5 obviously inhibited the proliferation of HepG2 cell line through inducing apoptosis. HIGHLIGHTS Focusing on coumarin and aryl hydrazide-hydrazone possess significant biological properties. We reported the preparation of coumarin hydrazine-hydrazone hybrids and evaluated their effects against hepatocellular carcinoma cell lines HepG2 and LH86. The hybrid compounds exhibited high potency against HepG2 and LH86. Flow-cytometry and caspase-3/7 expression analysis revealed that the hybrid compounds induced apoptosis in HepG2 cells. GRAPHICAL ABSTRACT

Cytotoxic potential of Commicarpus plumbagineus extracts against liver cancer cell lines through In-Vitro and In-Silico methods

Hepatocellular carcinoma holds the fifth position in terms of worldwide cancer prevalence. The challenges posed by drug adverse effects and resistance associated with existing anticancer therapies underscore the importance of exploring natural sources for potential solutions. This study assessed the in-vitro cytotoxicity of a range of solvent extracts (n-hexane, ethyl acetate, and methanol) against liver cancer cell lines using (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) (MTT) assay. The bioactive extract was also examined for its impact on cell migration and subjected to in-silico predictions targeting 14 different protein targets. The results indicated that only the ethyl acetate (F2) extract was cytotoxic. The IC50 values for the F2 were 300, 320 and 318 μg/mL against HepG2, HuH7, and normal HUVECs cell lines, respectively. A significant reduction in the % relative migration of cells following treatment with 87.5 μg/mL of F2 extract was observed. The apoptotic potential of F2 was seen on HepG2 cells using the DAPI and AO/EtBr staining. The F2 extract underwent GC–MS analysis, uncovering the existence of 23 phytocompounds, which were subsequently employed in molecular docking studies. Loperamide, á-Sitosterol, and stigmasterol exhibited the highest binding affinity (−10.90 kcal/mol) for 4WEV and 4NOS. These phytochemicals from the F2 extract hold potential as promising drug candidates for liver cancer, subject to further validation.

Spectroscopic, biological activity, molecular docking and hydrogen storage studies of tetrazole-thione complexes

Six nano-tetrazole-thione complexes of the type [M(MmtzS)2] (MII = Ni (1); Zn(4); Cd (5) and Hg (6)} and [M2(MmtzS)4] (MII = Pd (2) and Pt (3)} were synthesized by treating by the reaction of one equivalent mole of inorganic salts {NiCl2·6H2O; Na2PdCl4; K2PtCl4; ZnCl2; CdCl2 and HgCl2} with two equivalent moles of 1-methyl-1,2,3,4-tetrazole-5-thiol (HMmtzS). The synthesized compounds were obtained through investigation by several physicochemical and spectroscopic techniques. XRD and SEM investigations indicate the crystalline and morphological structural studies of the complexes. Additionally, the MmtzSH ligand and their complexes were tested as antimicrobial agents against four pathogenic bacteria species (Escherichia coli, Klebsiella pneumonia, staphylococcus epidermidis, and Staphylococcus aureus), the results showed that the Ni(II) complex displayed the uppermost activity with the region inhibition within 19 mm(activity index = 72%) to 27 mm (activity index= 96 %) compared to the standard antibacterial drug and other complexes. The cytotoxic effect study was applied to colon carcinoma (CaCo2), and hepatoblastoma (HepG2) cell lines, using the MMT method for complexes (1–4). The Ni(II) complex has the highest activity among all tested compounds. In addition, the complexes 4–6 were chosen for hydrogen storage ability. The findings demonstrate the hydrogen-storing capacity of all tested complexes, with the zinc complex demonstrating the highest capacity at 40 bar and 173 K with 0.99 wt.%.