Carcinoma HepG2 Research Articles

Sansevieria: An evaluation of cytotoxic activity in reference to metabolomic and molecular docking studies

Sansevieria trifasciata Prain. and Sansevieria suffruticosa N.E.Br. were selected to evaluate their cytotoxic activity against colon (CACO2), lung (A-549) and liver (HepG-2) carcinoma cell lines. Results indicated that S. suffruticosa N.E.Br. showed a significant cytotoxic effect on CACO2 with IC50= 30.9 ± 0.72 μg/ml. Evaluating the phenolic and flavonoid contents, S. suffruticosa N.E.Br. has higher total phenolic and flavonoid contents than S. trifasciata Prain. The phenolic content was estimated using HPLC detecting the presence of apigenin-7-glucoside and cinnamic acid only in S. suffruticosa N.E.Br. with p-hydroxybenzoic acid and p-coumaric acid being the major compounds. While, catechin and kaempferol are the major compounds detected in S. trifasciata Prain. Phytochemical investigation of ethyl acetate fractions of both species results in isolation of chlorogenic acid, kaempferol, quercetin, and catechin from S. trifasciata Prain. and apigenin-7-glucoside and rutin from S. suffruticosa N.E.Br. Isolated compounds are identified using recent spectroscopic methods. All compounds are isolated for the first time from these species. Metabolomic profiling indicates the presence of phenolic acids, flavonoids and saponins in the alcoholic extracts of the two species. In addition, molecular docking study was done for further investigation of the possible targets involved in the cytotoxicity of the alcoholic extracts of the two Sansevieria species. The ability of some phenolic compounds to interact with EGFR cancer target site rationalizes the cytotoxic activity of S. suffruticosa N.E.Br. alcoholic extract as proven by their docking pattern and docking score.

Redounding of Cuscuta chinensis Lam. on BxPC-3, HepG2, and U2OS Human Cancer Cell Lines

Objective: The present study was designed to investigate in vitro cytotoxic effect of aqueous extract from whole Cuscuta chinensis on human hepatocellular carcinoma (HepG2), biopsy xenograft of pancreatic carcinoma line-3 (BxPC-3), and children human bone osteosarcoma cell line (U2OS). Materials and Methods: The anticancer effectiveness of the methanol-watery extract of C. chinensis Lam. was determined by using methyl tetrazolium bromide test (MTT) assay against cancer cells by using suspensions of BxPC-3, HepG2, and U2OS cell lines. The inhibitory concentration (IC50) was tested for each cancer cell line. BxPC-3, HepG2, and U2OS cell line death percent after incubation with extract for 24, 48, and 72-hours interval was compared with cisplatin death percent. Results: The results showed that the IC50 of Cuscuta extract for BxPC-3, HepG2, and U2OS cell lines was 13, 6.5, and 0.73 μg/mL, respectively. The HepG2 cell line death%, when treated with 50 μg/mL Cuscuta extract at 24, 48, and 72-hour time interval, was 90.41, 91.45, and 92.93%, while cells were treated with 15 μg/mL cisplatin, the death percent was 88.8, 93.7, and 96.61%, respectively. The BxPC-3 cell line death%, when treated with 50 μg/mL Cuscuta extract, was 51.46, 83.37, and 91.28%, respectively, and when treated with 15 μg/mL cisplatin was 81.64, 88.02, and 96.67%, respectively. The U2OS cell line death%, when treated with 50 μg/mL Cuscuta extract, was 69.43, 69.75, and 88.89%, and was 74.1, 84.61, and 93.39%, respectively, when treated with 15 μg/mL cisplatin. Conclusion: The methanol-watery extract of C. chinensis Lam. may have a potential role as an adjunct therapy for cancers in the future.

Quinoline-pyrimidine hybrid compounds from 3-acetyl-4-hydroxy-1-methylquinolin-2(1H)-one: Study on synthesis, cytotoxicity, ADMET and molecular docking

Some novel 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized from α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. The purity and structure of the obtained products have been confirmed by thin layer chromatography, IR, 1H NMR, 13C NMR, HSQC, HMBC and MS spectra. All the synthesized of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-methylquinolin-2(1H)-ones 6a-i were screened for their in vitro cytotoxic activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values equal to 1.33 μM. Compounds 6a-g exhibited weak or insignificant activity with liver cancer cell lines HepG2, while compounds 6a and 6g had more powerful activity in this sequence, with IC50 values equal to 47.99 and 89.38 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that two hydrogen bonding interactions in the binding pocket, as potential ligand binding hot-spot residues for compounds 6b and 6e, may be one of the mechanisms of action responsible for the higher cytotoxic effect on HepG2 and KB cells.

Abstract 6562: Design, synthesis and anticancer properties of trans-cinnamaldehyde and curcumin based scaffolds compounds

Abstract Cinnamaldehyde and curcumin scaffolds are known for their anticancer potential via reactive oxygen species (ROS) generation and cellular damage. Herein, we synthesized a set of heterocyclic compounds build on the naturally-occurring trans-cinnamaldehyde and curcumin scaffolds and assessed their antiproliferative/cytotoxic properties against hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF-7) and colorectal cancer cells (HCT-116). The general structure of the synthesized compounds comprised 2-(4-fluorophenyl)-4-imidazolone nucleus attached to a 2-phenylpropylidene moiety. The imidazolone's N1 diversity point was attached to a variety of groups that are different in steric as well as electronic properties. Compounds FC01, FC09, FC11, FC12, FC14, FC30 and FC37 (groups attached to N1 diversity point are phenyl, methyl, 4-methylpiperazinyl, n-propyl, 4-hydroxyphenyl, 2-furylmethyl, and 4-methoxyphenyl, respectively) showed considerable cytotoxicity with IC50 ranging from 0.1 to 11.9 µM against MCF-7, HepG2, and HCT-116 cells. Within one hour of exposure to the IC50's of compounds FC09, FC12 and FC31, total ROS was significantly increased to 143.3±1.2%, 158.2±8.6% and 138±9.3% of control. After 2 hours of exposure, compounds FC09, FC12, FC14, FC30 and FC31 significantly raised the total ROS by 148.3±2.1%, 144.2±5.9%, 112±3.1%, 134.8±10.3% and 140.7±5.7%, respectively. Interestingly, all compounds under investigation significantly raised the intracellular ROS within 1.5 h of exposure. After 24 h of exposure, only compounds FC01, FC07, FC30, and FC31 kept the intracellular level of ROS significantly higher than control cells (111.1±3.6, 113.8±4.3%, 110.4±2.2%, and 117.7±7.5%, respectively). On the other hand, the ROS level within cells treated with the IC50 of compounds FC09 and FC12 for 24 h was significantly lower than control cells (85.7±1.3 and 68.4±4.7, respectively). Apoptosis/necrosis differential assessment using annexin-V/FITC with PI as a counterstain coupled with flow cytometric analysis, showed that compounds FC01, FC09, and FC12 induced significant apoptosis as well as necrosis by 2-5 folds compared to control cells. Compound FC14 failed to induce any significant apoptosis or necrosis. In conclusion, trans-cinnamaldehyde and curcumin scaffold-based compounds under investigation, particularly FC01, FC09 and FC12 might represent promising candidates in anticancer molecules for further optimization. Citation Format: Abdel-Sattar M. Omar, Ahmed M. Al-Abd. Design, synthesis and anticancer properties of trans-cinnamaldehyde and curcumin based scaffolds compounds [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6562.

HEPATOPROTECTIVE ACTIVITY OF ETHANOLIC STEM BARK EXTRACT OF KNEMA ATTENUATA (HOO K. F. AND THOMSON) WARB

Objective: To investigate the hepatoprotective activity of ethanolic stem bark extract (ESBE) of Knema attenuata against carbon tetrachloride (CCl4) induced hepatotoxicity in Wistar rats using both in vivo and in vitro models.
 Methods: Animals were treated orally with ESBE (250 mg kg-1 and 500 mg kg-1) once daily for 6 d and CCl4 on the 4th d. On the 7th d, animals were sacrificed and the blood samples were collected to measure the serum levels of biochemical parameters, whereas the liver homogenates were utilized for estimating the antioxidant defense. The hepatoprotective efficacy of the extract was further ensured in vitro using human liver hepatocellular carcinoma (HepG2) cell line against CCl4 induced toxicity. The cell line viability was determined using 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.
 Results: ESBE effectively reduced (p<0.001) the elevated serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and Alkaline phosphatase (ALP) when compared to the toxicant control group. ESBE 500 mg kg-1significantly raised the antioxidant defense (p<0.0001) by reducing the malondialdehyde (MDA) level and enhancing hepatic reduced glutathione (GSH) level in comparison to the CCl4 control group. The in vitro effect was investigated using CCl4 exposed HepG2 cells. Pretreatment with ESBE showed a dose-dependent increase in percentage cell viability ranged between 44 to 57% at 12.5-100 μg ml-1concentrations (p<0.001, when compared to the control cells). 
 Conclusion: Present study confirms the hepatoprotective activity of the stem bark extract of K. attenuata against CCl4‑induced liver damage.

In Vivo/In Vitro Properties of Novel Antioxidant Peptide from Pinctada fucata.

Due to the potential of antioxidants to scavenge free radicals in human body, it is important to be able to prepare antioxidant peptides that meet the industrial requirements for cosmetics and food. Here, we determined in vivo/in vitro activities of antioxidant peptide from P. fucata (PFAOP) prepared by bio-fermentation method. The antioxidant property test results showed the DPPH, hydroxyl, superoxide radical-scavenging, and cellular antioxidant activity. EC50 values of PFAOPs were 0.018 ± 0.005, 0.126 ± 0.008, 0.168 ± 0.005, and 0.105 ± 0.005 mg/ml, respectively, exhibiting higher antioxidant activities than glutathione (p < 0.05). Moreover, anti-proliferation and cytotoxicity activity results illustrated PFAOP has a potent anti-proliferative activity against HepG2, Caco-2, and MCF-7 carcinoma cells with no cytotoxicity. Moreover, the protocols we developed in this work demonstrated several excellent advantages in PFAOP preparation compared to enzymatic hydrolysis or chemical synthesis methods and provide a theoretical foundation for higher-value application of marine-derived functional peptides.

Liquid chromatography high-resolution mass spectrometry analysis, phytochemical and biological study of two aizoaceae plants: A new kaempferol derivative from Trianthema portulacastrum L.

Background: Natural remedies used for the treatment of liver diseases have a major concernworldwide. Objectives: Evaluation of the cytotoxic potential of successive fractions of two Aizoaceae plants; Trianthema portulacastrum L. and Aizoon canariense L. against human hepatocellular carcinoma (HepG2) cell lines. Moreover, metabolomic profiling of the successive fractions of both plants was carried out. Materials and Methods: Cytotoxic activity of successive fractions of the two plants against hepatocellular carcinoma (HCC) HepG2 cell lines were evaluated using viability assay, whereas metabolomic profiling was carried out using Liquid Chromatography High-Resolution ElectroSpray Ionization Mass Spectrometry (LC-HR-ESI-MS). Results: Significant cytotoxic activity of the n-hexane and n-butanol extracts of A. canariense (24.7 ± 3.5 and 55.3 ± 4.9 μg/mL, respectively) is recorded. On the other hand, metabolomic profiling of both plants resulted in dereplication of 27 metabolites belonging to different chemical classes; for example, sterols, flavonoids, diterpenes, triterpenes, tetraterpenes, alkaloids, lignans, hydrocarbons, and nucleosides. Phytochemical study of the biologically active fractions resulted in the isolation of one new compound; kaempferol-3-O-(2''-O-β-D-glucopyranosyl)-6''-O-E-feruloyl-β-D-glucopyranosid (T1). Biological testing of the isolated compounds indicated significant activity of T1 against HCC (IC50 =7.19 ± 0.27 μg/mL). Conclusion: Phytochemicals isolated from T. portulacastrum L and A. canariense L. may be responsible for their cytotoxic activity against HCC HepG2 cell lines.

Evaluation of cytotoxicity and antioxidant potential of bael leaf (Aegle marmelos) on human hepatocellular carcinoma cell line

Background: Aegle marmelos (Bael) is one of the important medicinal plants for curing human diseases. Nevertheless, the information about the cytotoxic and antioxidant effects of Bael leaf is not much. Objectives: The objective of this study is to evaluate the cytotoxicity and antioxidant activity of Bael leaf in human hepatocellular carcinoma (HepG2) cell lines. Materials and Methods: Bael leaves extract was prepared by 80% (v/v) aqueous ethanol and measured for total phenolic compound and antioxidant capacity. The ability of ethanolic Bael leaf extract to inhibit hepatic cancer cells (HepG2 cell) growth was evaluated by determining the percentages of cell viability. The levels of intracellular reactive-oxygen species (ROS) and lipid peroxidation were determined. Results: Bael leaf extract demonstrated the potentiality to inhibit the cancer cell growth with a 50% inhibitory concentration (IC50) at 50 μg/ml and 72 μg/ml after 24 h and 48 h incubated times, respectively. The total phenolic content and antioxidant capacity of ethanolic extract were 218.33 ± 43.81 mg gallic acid equivalent/g of dry extract and 33.62 ± 3.07 mg Trolox equivalent antioxidant capacity/g of dry extract, respectively. At the lowest concentration of Bael leaf extract, it was found that Bael leaf extract shows the antioxidant activity by the ability to lowering the level of ROS and malondialdehyde in HepG2 cell. Conclusion: Bael leaf has a high antioxidant component, which is beneficial and can be developed as new therapeutic uses. However, further studies on the benefits of Bael leaf should be performed for better realizing and effective use soon.

Cytotoxic and immunomodulatory phenol derivatives from a marine sponge-derived fungus Ascomycota sp. VK12

Chemical investigation of the marine-derived endophytic fungus Ascomycota sp. VK12 resulted in isolation and identification of a new compound, (3R)-(3′,5′-dihydroxyphenyl)butan-2-one (1) and five known ones: AGI-7 (2), sescandelin (3), sescandelin-B (4), 4-hydroxybenzaldehyde (5), and hydroxysydonic acid (6). The absolute configuration of 1 was determined by time-dependent density functional theory electronic circular dichroism, specific optical rotation, and NMR calculations. Compounds 1 and 2 showed cytotoxicity towards HepG2, MCF-7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 48.6 to 96.5 µM. Compounds 1, 2, 4–6 displayed NO inhibitory effects in LPS-stimulated BV2 cells, with IC50 values in a range from 24.2 to 76.5 µM. Compound 2 further inhibited PGE2 overproduction, with an IC50 value of 25.3 µM. The inhibitory effects of 2 towards NO and PGE2 overproduction were found to have a close relationship with its suppression of iNOS and COX-2 protein expression, respectively.

Chemical profiling of Thevetia peruviana leaves cytotoxic active extracts enhanced by microemulsion formulation

BackgroundNatural products played an essential role as a complementary cytotoxic agent avoiding complications of other therapies. In phytoformulation research, herbal drugs of nano-size have attracted more attention for more bioavailability and less active dose. We aim in this work to introduce new non-mutagenic cytotoxic agent from Thevetia peruviana leaves extracts and potentiate the activity by loading upon microemulsion formulations as an advanced mode of drug delivery system.ResultsThevetia peruviana toxicity test revealed its safety (LD50 = 3.083 g/kg). In vivo genotoxicity tests measuring chromosomal aberrations were done to prove non-mutagenicity of the plant for both somatic and germ cells. The plant showed antioxidant activity with 121.215, 128.925, and 120.098 mg/g extract, calculated as Trolox equivalent (TE/g) for DPPH, ABTS, and FRAP assays, respectively. Successive extracts of the plant were incorporated in microemulsion formulations (MEF) and characterized for their electrical conductivity, poly-dispersity index, and in vitro drug release action. Cytotoxic activity of successive extracts was investigated against breast MCF7 and liver HEPG2 carcinoma cell lines before and after loading upon MEs. Enhancement in activity was detected for both pet. ether and ethanol MEFs, as IC50 of pet. ether extract decreased from 25 to 6.5 μg/ml against MCF7 cell line, while ethanol formulation recorded IC50 = 3.58 μg/ml against HEPG2 cell line after showing no activity of the extract at the tested concentrations.Regarding metabolites of polar fraction, total ethanol extract was estimated for total phenolic and flavonoid contents to record 47.7941 mg GAE/g calculated as gallic acid equivalent and 32.7667 mg CE/g measured as catechin equivalent, respectively. HPLC analysis for polar fraction recorded twelve compounds identified according to the available authentics with rutin the major flavonoid (7.33 mg/g) and rosmarinic acid (13.48 mg/g) the most abundant phenolic acid. Phytoconstituents of non-polar fraction were investigated after saponification of pet. ether extract using GC/MS analysis revealed the identification of 88.02% of the total unsaponifiable matter and 89.17 % of the total saponifiable matter.ConclusionThevetia peruviana is a safe cytotoxic agent. Microemulsion formulations of active extracts potentiate the cytotoxic actions against HEPG2 and MCF7 cell lines with better bioavailability and less medicinal doses.

Cancer Chemopreventive Properties of Sulfated Enterolobium cyclocarpum Extract

Enterolobium cyclocarpum (EC) is an edible plant and a gum source for food industries. Its sulfated polysaccharide extract (SEC) was examined for cancer chemopreventive properties to estimate its anti-tumor activity. The modulation of carcinogen metabolism and the antioxidant activity revealed that SEC is a potent tumor anti-initiator since it inhibited cytochrome P450-1A (CYP1A) and induced carcinogen detoxification enzyme glutathione-S-transferase. SEC is also a weak scavenger for hydroxyl and peroxyl radicals. SEC was found to modulate macrophage functions into an anti-inflammatory pattern, where it enhanced macrophage proliferation and phagocytosis of fluorescein isothiocyanate-lipopolysaccharide (FITC-LPS). In addition, SEC strongly inhibited the nitric oxide (NO) generation in LPS-stimulated macrophages and induced the binding affinity of FITC–LPS to macrophages. SEC exhibited specific cytotoxicity against human hepatocellular Hep G2 carcinoma cells. SEC disturbed the cell cycle phase, as indicated by the concomitant arrest in S- and G2/M-phases that was associated with necrosis induction. A short-term initiation model for liver cancer was prepared using diethylnitrosamine (DEN) in rats. SEC inhibited the DEN-histopathological findings and reduced both CYP1A and the tumor initiation marker placental glutathione S-transferase (GSTP). Taken together, SEC could be used as an alternative gum in health food industries to provide cancer prevention in high-risk populations.

Spirulina maxima L-asparaginase: Immobilization, Antiviral and Antiproliferation Activities.

L-asparaginase (L-AsnA) enzyme has gained significant attention in the food, biocatalysts and pharmaceutics industry. It (L-AsnA) has been widely used in food processing industries as a promising acrylamide mitigating agent and as a therapeutic agent in the treatment of certain human cancers. Based on US Patent (4,433,054; 1984), L-asparaginase (L-AsnA) enzyme is immobilized by admixing the active enzyme on the polysaccharide to be in a gel form. The storage stability of immobilized L-AsnA enzyme and its anti-proliferation and antiviral activity were determined. In the present study, S. maxima was cultured at large scales (300 liter) for the production of enough extracellular L-asparaginase (L-AsnA) using modified (high N concentration) Zarrouk medium as we reported in a previous study. L-AsnA was immobilized on natural polymers, as agar cake beads, agarose pieces and gelatin blocks, in order to evaluate the efficiency of physical entrapment techniques. Anti-proliferation properties of L-AsnA against lung carcinoma A549, hepatocellular carcinoma Hep-G2 and prostate carcinoma PC3 human cancer cell lines were assessed by the MTT cell viability method. In addition, the antiviral activity against Coxsackie B3 (CSB3) Virus was assessed. The highest L-AsnA immobilized activity and immobilization yield were achieved with agar cakes bead. The purified S. maxima L-AsnA showed good antiviral activity against Coxsackie B3 (CSB3) Virus in a dose-dependent manner with an IC50 value 17.03 μg/ml. The antiviral mode of action is presumably due to their capability of inhibiting attachment, blocking the adsorption and penetration event of the viral replication cycle with 89.24%, 72.78% and 72.78%, respectively. Also, S. maxima L-AsnA showed anti-proliferation effect against lung carcinoma A549, hepatocellular carcinoma Hep-G2 and prostate carcinoma PC3 human cancer cell lines, with an IC50 of 22.54, 24.65 and 56.61 μg/ml, respectively. It is interesting to favor L-asparaginase of S. maxima which showed antiviral activity and anti-proliferation effect against different types of human cell lines. Thus, S. maxima microalgae might be a good source for L-AsnA enzymes and can be immobilized on natural polymers.

Cytotoxicity influence of new chitosan composite on HEPG-2, HCT-116 and MCF-7 carcinoma cells

Chitosan/aroylhydrazine composite were synthesized in hydrogel form in which aroylhyrazines, heteroaroylhydrazines as well as p-tolylsulphonylhydrazine embedded in the cross linked Chitosan/oxalic acid network. Their structures were characterized by (elemental analysis, FT-IR, 1H NMR, and XRD). Antimicrobial behavior and Cytotoxicity screening of the examined compounds against breast, colon and hepatocellular cancer were investigated. The obtained data revealed that the examined compounds have promising cell growth inhibitory effect on the cell lines as compared to standard. Also, some of the newly synthesized derivatives had shown better antibacterial and antifungal activities, comparing with that of the parent chitosan.

Synthesis and Anticancer Activity of Functionalized Thieno[2,3-d]pyrimidine Compounds and Their Triazinyl and Tetrazinyl Derivatives

New thienopyrimidine derivatives substituted with amino and hydrazinyl side chains were synthesized starting with 2-hydrazinyl substituted thienopyrimidine as a key compound. The newly synthesized compounds were studied for their anticancer activity against prostate cancer (PC3), lung carcinoma (A549), and hepatocellular carcinoma (HepG2) cell lines. Benzothienopyrimidine derivatives incorporating thioxoethanethioamide, pyrimidotetrazine carbothioamide, and hydrazinylglycine moieties exhibited high activities against PC3 or A549 cell lines. In addition, the thienopyrimidotriazine derivatives and their thienopyrimidinone analogues were preferentially active against the two cell lines. A number of the synthesized compounds also revealed moderate activities against PC3 and A549 cell lines.

One-Pot Synthesis of 5-(Het)Aryl 8-Aminoquinoline Amide Derivatives as Potential Antibacterial / Cytotoxic Agents

Background: The 8-Aminoquinoline (8-AQ) framework has attracted particular attention in the discovery and development of antimalarial and anti-bacterial agents or drugs. However, the clinical uses of 8-AQ based drugs are often associated with toxic side effects such as methemoglobinemia and hemolytic anemia with deficiency in Glucose-6-Phosphate Dehydrogenase (G6PD) Activity. The 4-aryl- 8-amino(acetamido)quinoline derivatives, on the other hand, have shown antiproliferative activities against cancer cell lines. These reports prompted us to assess the antibacterial and cytotoxic activities of a series of compounds based on 5-aryl 8-aminoquinoline amide scaffold. Methods: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized via a one-pot ultrasound-assisted method using a C-5 selective halogenation of quinoline derivatives followed by Pd/C-catalyzed Suzuki-Miyaura coupling with (het)aryl boronic acids. All these compounds were evaluated for their in vitro antibacterial activities against representative Gram-(+) and Gram-(-) strains including Escherichia coli, Pseudomonas aeruginosa, Klebsiella species and Staphylococcus aureus. Three compounds were further tested for cytotoxicities in vitro against breast adenocarcinoma (MCF7) and Hepatocellular Carcinoma (HepG2) along with non-cancerous human embryonic kidney (HEK293) cell lines. Results: All these compounds demonstrated moderate to good antibacterial activities against the four organisms used. In vitro assay results revealed that three compounds showed good activities against Gram-(+) strains and Gram-(-) strains and one was comparable to ciprofloxacin and pefloxacin. These three compounds were further tested for their cytotoxic properties against MCF7 and HepG2 cell lines. One of them showed IC50 value comparable to doxorubicin when tested against HepG2 cell lines. However, none of these compounds showed any significant effects when tested against HEK293 cells indicating their selectivity towards the growth inhibition of cancer cells. Conclusion: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized and evaluated for antibacterial and cytotoxic activities. Several of these compounds showed promising antibacterial and cytotoxic activities when tested in vitro suggesting that the present class of compounds may be of interest for the identification of new and potential antibacterial / cytotoxic agents.

Construction of higher-order cellular microstructures by a self-wrapping co-culture strategy using a redox-responsive hydrogel

In this report, a strategy for constructing three-dimensional (3D) cellular architectures comprising viable cells is presented. The strategy uses a redox-responsive hydrogel that degrades under mild reductive conditions, and a confluent monolayer of cells (i.e., cell sheet) cultured on the hydrogel surface peels off and self-folds to wrap other cells. As a proof-of-concept, the self-folding of fibroblast cell sheet was triggered by immersion in aqueous cysteine, and this folding process was controlled by the cysteine concentration. Such folding enabled the wrapping of human hepatocellular carcinoma (HepG2) spheroids, human umbilical vein endothelial cells and collagen beads, and this process improved cell viability, the secretion of metabolites and the proliferation rate of the HepG2 cells when compared with a two-dimensional culture under the same conditions. A key concept of this study is the ability to interact with other neighbouring cells, providing a new, simple and fast method to generate higher-order cellular aggregates wherein different types of cellular components are added. We designated the method of using a cell sheet to wrap another cellular aggregate the ‘cellular Furoshiki’. The simple self-wrapping Furoshiki technique provides an alternative approach to co-culture cells by microplate-based systems, especially for constructing heterogeneous 3D cellular microstructures.

Structural characterization, antiproliferative and immunoregulatory activities of a polysaccharide from Boletus Leccinum rugosiceps

A homogeneous water-soluble flaky polysaccharide named LRP-1 (18.82 kDa) was extracted and purified from the rare edible and medicinal fungi Leccinum rugosiceps. The structure characterization of LRP-1 was analyzed by GPC, GC, GC–MS, FT-IR, SEM, 1D/2D NMR, and its antitumor and immunoregulatory activities were determined. The results show that LRP-1 is a new polysaccharide with a backbone which is mainly composed of →1-α-D-Fucp-3→, →1-α-D-Rhap-3→, →1-β-D-Glcp-6→, →1-β-D-Glcp-3→, →1-α-D-Glcp-4→, →1-β-D-Galp-6 → and →1-α-D-Manp-6→. Results of MTT assay show that LRP-1 inhibit the growth of human hepatoma cells HepG-2 and human breast carcinoma MCF-7 cells in vitro. LRP-1 could also induce the secretion of NO and immune factors (IL-6 and TNF-α) of RAW264.7. This study suggests that LRP-1 has potential to be used as nutraceutical food with antitumor and immunoregulatory activities.

Exploration of aurora B and cyclin-dependent kinase 4 inhibitors isolated from Scorzonera tortuosissima boiss. and their docking studies

Background: Flavonoids are components of the daily human diet (fruits and vegetables), and it has been shown to inhibit several kinase enzymes. Due to its kinase inhibitory activity, they are expected to be of great importance in the discovery of new anticancer drugs. Objectives: The objective was to study the cytotoxicity, kinase inhibitory activity, and docking of the isolated aglycones. Materials and Methods: Ultraviolet, high-performance liquid chromatography (LC), nuclear magnetic resonance, and LC-mass spectrometry were used for the identification of the isolated metabolites. Antiproliferative (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and radiometric protein kinase (PK) assays were used to measure the cytotoxicity and PK inhibitory effect of the isolated flavonoids. The docking study on both Aurora B and cyclin-dependent kinase 4 (CDK4)/CycD1 was performed by molecular operating environment (MOE). Results: Luteolin (1), quercetin (2), myricetin (3), apigenin-7-O -β-D-glucopyranoside (4), and kaempferol-7-O -β-D-glucopyranoside (5) were isolated from Scorzonera tortuosissima . Quercetin and myricetin exhibited the highest cytotoxicity against the Michigan Cancer Foundation-7 (MCF-7) (IC50: 5.56 and 7.14 μM, respectively) and against human hepatocellular carcinoma (HepG2) (IC50: 8.61 and 10.31 μM, respectively), while compounds luteolin and apigenin-7-O-β-D-glucopyranoside showed the least cytotoxicity compared to doxorubicin against to MCF-7 and HepG2 (IC50: 2.24 ± 0.85 and 1.82 ± 0.34 μM, respectively). The radiometric PK assay was applied for measurement of kinase inhibitory activity against Aurora B, CDK4/D1, cancer Osaka thyroid, IGF1-R, and FAK kinases, where the aglycone myricetin showed the highest inhibitory activity against Aurora B (IC50: 2.82 μM) and against CDK4/cyclin D1 (IC50: 3.16 μM), while the isolated glycosides 4 and 5 revealed the lowest activity. Docking of the most active compounds 1, 2, and 3 against Aurora B and CDK4/cyclin D1 confirmed its cytotoxic profile. Conclusion: The isolated flavonoids were firstly isolated from S. tortuosissima . The hypothetical mechanism of cytotoxic activity of 1, 2, and 3 on Aurora B and CDK4/cyclin D1 kinases was estimated by in silico study with these enzymes using MOE program.

Expeditious Sonochemical Synthesis of New 1,8-Naphthyridine Derivatives and their Inhibitory Activity on HepG2 Cell Line

Abstract: A new series of 2-phenyl-1,8-naphthyridine derivatives were synthesized via traditional heating and under ultrasonic irradiation to run out comparative study and confirm the utility of the green chemistry in organic synthesis. An improvement in the rates and yields were observed upon carrying out the reactions under environmentally benign protocol. The newly produced compounds were scanned in vitro for their adverse activity on HepG2 (Human liver) carcinoma cell lines. Results revealed that the tested compounds possess an inhibitory effect on the growth of HepG2 carcinoma cells. The naphthyridinyl pyridine derivatives 4c and 5c showed significant cytotoxic activity. The oxo-pyridine derivative4c was more potent than the reference drug doxorubicin (DOX), while the imino-pyridine derivative 5c showed slight reduction in the potency. On the other hand, Mannich bases (2a,c,d,e) showed good activity and the styryl derivatives (6b-d) showed moderate activity when compared to (DOX).

An Efficient And Catalytically Free Chemical Transformation of Pyrimidin-2(1H)-one to 2-(N-Arylamino)pyrimidines and their in vitro Cytotoxicity Evaluation

With the aim to develop an efficient strategy to synthesize pyrimidine derivatives bearing diversely substituted amines involves four step linear protocols started with Biginelli multi-component reaction leading to dihydropyrimidines which passing throug multistep sequantial process containing oxidation, chlorination and catalytically free transformation of pyrimidin-2(1H)-one to 2-(N-arylamino)pyrimidines, were evaluated for cytotoxicity study against human cancer lines HCT-116, Hep-G2 and QG-56. Compound 4j exhibit significant anticancer activity showed against: human hepato carcinoma (Hep-G2) and human colon carcinoma (HCT-116) serve as a excellent lead molecule for the generation of various promising targets.