Human Cervix Carcinoma Cell Line Research Articles

Synthesis and cytotoxicity study of novel 3-(triazolyl)coumarins based fluorescent scaffolds

Recently a choice of fluorescent bioimaging probes have been developed as medical diagnostic tools. Herein, we have introduced a series of coumarin-based target specific probes for cancer theranostic application which play a dual role in the field of both diagnosis and therapy. A fluorogenic version of 1,3-dipolar cycloaddition between azides and alkynes (DBCO) has been introduced to develop the triazolylcoumarin based fluorescent scaffolds. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human epitheloid cervix carcinoma (HeLa) cell line. It was established that triazolylcoumarins (5c and 5d) are having electronegative substitution in the benzene ring displayed most effective anticancer profile in both the cell lines. Compounds 5a and 5d exhibited maximum quantum yield and strong cellular uptake in the MCF-7 cell line.

Synthesis of Novel Chiral Sulfonamide‐Bearing 1,2,4‐Triazole‐3‐thione Analogs Derived fromD‐andL‐Phenylalanine Esters as Potential Anti‐Influenza Agents

Novel enantiopure 1,2,4-trizole-3-thiones containing a benzensulfonamide moiety were synthesized via multistep reaction sequence starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The chemical structures of all compounds were characterized by elemental analysis, UV, IR, (1) H NMR, (13) C NMR, 2D NMR (HETCOR), and mass spectral data. All compounds were tested in vitro antiviral activity against a broad variety of DNA and RNA viruses and in vitro cytostatic activity against murine leukemia (L1210), human T-lymphocyte (CEM) and human cervix carcinoma (HeLa) cell lines. Although enantiopure 1,2,4-triazole-3-thione analogs in (R) configuration emerged as promising anti-influenza A H1N1 subtype in Madin Darby canine kidney cell cultures (MDCK), their enantiomers exhibited no activity. Especially compounds , , , , and (EC50 : 6.5, 6.1, 2.4, 1.6, 1.7μM, respectively) had excellent activity against influenza A H1N1 subtype compared to the reference drug ribavirin (EC50 : 8.0μM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC50 in the 12-53μM range. Compound and in (R) configuration were the most active compounds (IC50 : 12-22μM for and IC50 : 19-23μM for ). Chirality 28:495-513, 2016. © 2016 Wiley Periodicals, Inc.

Synthesis of novel anticancer ruthenium–arene pyridinylmethylene scaffolds via three-component reaction

A novel three components approach for the synthesis of bioactive Ru–arene pyridinylmethylene complexes has been developed using pyridine carboxaldehyde, amino pyridine and dichloro (p-cymene) ruthenium(II) dimer as starting materials. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human Epitheloid Cervix Carcinoma (HeLa) cell line. It was established that compounds [(η6-pcymene)RuCl(κ2-N,N-(3,5-dinitro-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4o), [(η6-pcymene)RuCl(κ2-N,N-N-(3,5-dibromo-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4c), [(η6-pcymene)RuCl(κ2-N,N-(3,5-dibromo-6-methylpyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4j) and [(η6-pcymene)RuCl(κ2-N,N-3(3-bromo-5-methyl-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4b) were significantly active against both the cell lines.

Synthesis and cytotoxic effects of SrAl_2O_4 persistent luminescence nanoparticles co-doped with Eu^2+/Dy^3+ ions

Persistent luminescence strontium aluminate nanoparticles co-doped with Eu2+ and Dy3+ were prepared by urea-assisted combustion synthesis. Different percentages of co-dopants were evaluated in order to optimize luminescence of the nanophosphor. Luminescence measurements showed that excitation of this green-emitting phosphor occurred within a wide range of wavelengths (254 – 460 nm) while the half-life time of persistent luminescence laid within the seconds regime. Presence of Dy3+ as the co-dopant enhanced the green emission in this interval of time, and the entire decay time occurred in minutes. Crystallinity and morphology were evaluated by X-ray diffraction (XRD) and transmission electron microscopy (TEM), respectively. Strontium aluminate co-doped with 1%Eu, and 1%Dy, and 1%Eu, and 3%Dy emitted an intense green signal and long decay time. These crystal nanophosphors displayed sizes of 18 nm and 22 nm, respectively. The cytotoxic effect of nanoparticles was determined by a cell viability test where the tri-methyl-tetrazolium reagent (MTT) was reduced only by metabolically active cells. Different concentrations of bare nanoparticles were tested in a 96-well plate containing 10, 000 cells per well of a human cervix carcinoma cell line (HeLa). Evaluation of cell viability by this cytotoxic assay showed that in most of the cases cell viability was higher than 60% after incubation with bare nanoparticles. Since our bare nanoparticles were not cytotoxic, these results open a broad field of biomedical applications for phosphorescent materials as cell biolabels and imaging research area.

Long-chain alkyl-substituted gentisic acid and benzoquinone derivatives from the root of Micronychia tsiramiramy (Anacardiaceae)

Abstract A new gentisic acid derivative named micronyc acid (1) and a new 1,4-benzoquinone derivative named micronone (2) have been isolated from the root of Micronychia tsiramiramy together with the known compounds gallic acid (3), methyl gallate (4), moronic acid (5), masticadienolic acid (6), and masticadienediol (7). The structures of 1 and 2 were established using MS and NMR. Compound 1 was tested for antiplasmodial activity in vitro against the chloroquine-resistant strain Plasmodium falciparum W2 and displayed moderate antiplasmodial activity in vitro with an IC50 value of 25.6 μ m. Compounds 1 and its acetyl derivative 1a were also tested for their cytotoxicity against the human cervix carcinoma cell line KB-3-1 and still showed moderate activity.

In vitro assessment of antiproliferative action selectivity of dietary isothiocyanates for tumor versus normal human cells.

Numerous epidemiological studies have shown beneficial effects of cruciferous vegetables consumption in cancer chemoprevention. Biologically active compounds of different Brassicaceae species with antitumor potential are isothiocyanates, present in the form of their precursors - glucosinolates. The aim of this study was to determine the selectivity of antiproliferative action of dietary isothiocyanates for malignant versus normal cells. Antiproliferative activity of three isothiocyanates abundant in human diet: sulforaphane, benzyl isothiocyanate (BITC) and phenylethyl isothiocyanate, on human cervix carcinoma cell line - HeLa, melanoma cell line - Fem-x, and colon cancer cell line - LS 174, and on peripheral blood mononuclear cells (PBMC), with or without mitogen, were determined by MTT colorimetric assay 72 h after their continuous action. All investigated isothiocyanates inhibited the proliferation of HeLa, Fem-x and LS 174 cells. On all cell lines treated, BITC was the most potent inhibitor of cell proliferation with half-maximum inhibitory concentration (IC50) values of 5.04 mmoL m-3 on HeLa cells, 2.76 mmol m-3 on Fem-x, and 14.30 mmol m-3 on LS 174 cells. Antiproliferative effects on human PBMC were with higher IC50 than on malignant cells. Indexes of selectivity, calculated as a ratio between IC50 values obtained on PBMC and malignant cells, were between 1.12 and 16.57, with the highest values obtained for the action of BITC on melanoma Fem-x cells. Based on its antiproliferative effects on malignant cells, as well as the selectivity of the action to malignant vs normal cells, benzyl isothiocyanate can be considered as a promising candidate in cancer chemoprevention. In general, the safety of investigated compounds, in addition to their antitumor potential, should be considered as an important criterion in cancer chemoprevention. Screening of selectivity is a plausible approach to the evaluation of safety of both natural isothiocyanates and synthesised analogues of these bioactive compounds.

Antiproliferative activities of several plant extracts from Turkey on rat brain tumor and human cervix carcinoma cell lines

Turkey has a wide range of flora and fauna due to its climatic diversity. Medicinal plants from Turkey have been used since ancient times for their primary health care. In this study, we examined antiproliferative activities of the extracts from Crataegus monogyna, Vitis vinifera, Glycrrhiza glabra, Alnus glutinosa L. gaertn, and Alcea rosea against rat brain tumor (C6) and human cervical cancer (HeLa) cell lines. The results were compared with the standard anticancer drugs 5-Flurouracil (5-FU) and Cisplatin. C. monogyna, V. vinifera and A. rosea exhibited better antiproliferative activity than 5-FU and cisplatin at 100-75 µg/mL concentrations, against C6 cell lines. On the other hand, C. monogyna and V. vinifera extracts showed considerable antiproliferative activity against HeLa cells compared with 5-FU and cisplatin at 100-75 µg/mL. It can be suggested that, C. monogyna, A. glutinosa L. gaertn, V. vinifera and A. rosea extracts could be developed as an anticancer drug.

Onosma aucheriana: A source of biologically active molecules for novel food ingredients and pharmaceuticals

The phenolic profile, antioxidant activity and cytotoxicity of O. aucheriana aqueous extract were investigated. HPLC-DAD (high performance liquid chromatography-diode array detector) technique was used to define the profile of phenolic compounds of the resultant extract. Antioxidant properties were evaluated using different methods, including phosphomolybdenum, free radical scavenging and lipid peroxidation assays. Rosmarinic, gallic and p-hydroxybenzoic acids were determined as the major phenolic compounds. Human rhabdomyosarcoma (RD), human cervix carcinoma (Hep2c) and murine fibroblast (L2OB) cell lines were used to examine the cytotoxicity of the extract. The IC50 (inhibitory concentration at 50%) values ranged from 25.54 to 40.34 µg/mL. These results suggest that this species may be considered as a valuable candidate for preparing new food and drug formulations.

Investigation of In vitro PDT Activities and In vivo Biopotential of Zinc Phthalocyanines Using 131I Radioisotope

Novel octylthio-containing asymmetrically substituted Zn(II) phthalocyanine (Zn(II)Pc1) and a symmetric derivative (Zn(II)Pc2) have been prepared to investigate the biological potential and ability to photosensitize singlet oxygen for photodynamic therapy applications. In this study, the singlet oxygen generation potential and in vitro photodynamic activities of these compounds have been tested. Both ZnPcs reveal to be very efficient singlet oxygen generators and promising PSs for PDT applications. In vitro PDT activities of the compounds were evaluated in EMT-6 murine mammary carcinoma and HeLa human cervix carcinoma cell lines. Moreover, Zn(II)Pc1 displayed the phototoxic effects in the mammary cancer cell line (6.25 μm concentration at 30 J/cm(2) light dose and 12.5 μm concentration at 20 J/cm(2) light dose), while Zn(II)Pc2 did not show any phototoxic effects both in two cell lines. Zn(II)Pcs were radiolabeled with (131) I in high yields. Biodistribution studies revealed that the radiolabeled Zn(II)Pc1 showed significant uptake in l. intestine, pancreas, brain, and ovary, while Zn(II)Pc2 has significant uptake in ovary and pancreas in normal rats. Hence, these Pcs derivatives could be promising candidate for tumor nuclear imaging.

131I–Zn–Chlorophyll derivative photosensitizer for tumor imaging and photodynamic therapy

In recent years, the photodynamic therapy studies have gained considerable attention as an alternative method to surgery, chemotherapy and radiotherapy which is commonly used to fight cancer. In this study, biological potentials of a benzyloxy bearing zinc(II) pheophorbide-a (Zn-PH-A) were investigated via in vivo and in vitro experiments. Zn-PH-A was labeled with 131I with high efficiency (95.3±2.7%) and its biodistribution studies were investigated on female Albino Wistar rats. The radiolabeled photosensitizer had been intravenously injected into the tail vein, and then the animals were sacrificed at 30, 60 and 120min post injection. The percent of radioactivity per gram of organs (%ID/g) was determined. The radiolabeled Zn-PH-A showed high uptake in ovary. In addition, photodynamic therapy studies of the photosensitizer were conducted in EMT6, murine mammary carcinoma and HeLa, human cervix carcinoma cell lines. For the photodynamic therapy studies, the cells with Zn-PH-A were exposed to red light (650nm) at the doses of 10–30J/cm2. The results showed that Zn-PH-A has stronger PDT effect in EMT6 than HeLa cell. Our present work demonstrates 131I-labeled photosensitizer as a bifunctional agent (PDT and nuclear imaging) which could be improved in future by using EMT6 growing tumor in nude mice.

Some studies in cyanine dyes incorporating pyridine rings endowed with pharmaceutical potency

We report the synthesis of new series of methine cyanine dyes 1, 3–13which have been obtained by the one-pot step reaction of quaternized heterocyclic compound 2 with benzenaminium salt 1 under various methodology technique. (E)-N-(((E)-2-Chloro-3-((phenylamino)methylene)cyclopent-1-enyl)methylene) benzenaminium chloride (1) was synthesized by the reaction of cyclopentanone with Vilsmeier-Haack reagent, then a mixture of an equimolar ratio of aniline: ethanol (1:1) was added to give the target compound. All the synthesized compounds were subjected to in vitro anticancer screening against two cell lines, human cervix carcinoma cell line and human breast carcinoma cell line. Some of these compounds were found to be equipotent or more potentthan commercial anticancer as an evident from the results.

Antioxidant and biological activity of chamomile extracts obtained by different techniques: perspective of using superheated water for isolation of biologically active compounds

In this work, extracts of chamomile (Matricaria chamomilla L.) ligulate flowers obtained by Soxhlet, microwave-assisted, ultrasound-assisted and subcritical water extraction were compared in respect to their bioactivity, more specifically antioxidant, antimicrobial and cytotoxic activity. In all obtained extracts, the content of total phenols and flavonoids was determined, indicating significant total extraction yields (49.70%) and total phenol content (151.45mg ECA/ml) in water extracts obtained under moderate subcritical conditions. By applying DPPH and Reducing Power Test subcritical water extraction showed superior free-radical scavenging ability in comparison to other investigated extraction techniques. Microbial properties of extracts were examined using eight selected indicator strains and for all extracts minimum inhibitory concentrations were in the range between 19.53 and 312.50μg/ml. Subcritical water extracts showed the highest activity against Escherichia coli (MIC=39.10μg/ml) and Aspergillus niger (MIC=39.10μg/ml). Cytotoxic effects of extracts were examined on human rhabdomyosarcoma cells (RD), cell line derived from human cervix carcinoma Hep2c (HeLa) and cell line derived from murine fibroblast (L2OB). On all three tested cell lines, subcritical water extracts demonstrated much better antitumor properties in comparison to extracts obtained by other techniques, with IC50 values for Hep2c, RD and L2OB cells 30.54, 20.54 and 19.65μg/ml, respectively.

A new xanthone derivative from twigs of Garcinia nobilis

Phytochemical investigation of the twigs of Garcinia nobilis led to the isolation of a new xanthone, named l-hydroxy-2,5-dimethoxyxanthone (1), together with 15 known compounds (2–16). The structures of the new and known compounds were established by means of spectroscopic methods and by comparison with previously reported data. The structure of compound 1 was confirmed by X-ray diffraction data. Compounds 1–16 were tested for their cytotoxic activity against human cervix carcinoma cell line KB-3-1. Compounds 5 and 11 showed moderate activity while others showed weak biological activity in these cytotoxicity assays. Compounds 4 and 9 were found to be inactive.

English

The aim of this investigation was to evaluate the phytochemical, antibacterial and cytotoxic activities of ethanol extract and hexane, dichlorometane, ethyl acetate and hydroethanolic fractions from Aristolochia galeata’s rhizomes. The minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) were evaluated by the broth microdilution assay to investigate the antibacterial activity of various extracts and fractions of A. galeata against Gram-positive and Gram-negative bacteria. The cytotoxicity of plant samples was evaluated in human cervix carcinoma cell line (HeLa) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The phytochemical study showed the presence of main secondary metabolites, steroids, flavonoids, coumarins and alkaloids. The ethanol extract and their fractions presented antimicrobial activity against Gram-positive bacteria, and Staphylococcus aureus was regarded the most sensitive strain with MIC of 250 µg/ml for the ethanol extract. The dichlorometane fraction showed bactericidal activity with the value of 1250 µg/ml and moderate cytotoxicity in front of the HeLa cell line tested (CC50 = 90 µg/ml). The results showed that A. galeata had effective antibacterial activity against Gram-positive bacteria and compounds extracted from A. galeata Mart. ex Zucc could be used as possible antimicrobials. The good antimicrobial activity and the low cytotoxicity presented by the hexane fraction can be promised for the new molecules with antibiotic activity. Key words: Aristolochia galeata, antibacterial activity, minimal inhibitory concentration, cytotoxic activity, phytochemistry.

In Vitro Evaluation of Zn–Norfloxacin Complex as a Potent Cytotoxic and Antibacterial Agent, Proposed Model for DNA Binding

A tetrahedral Zn(II) complex with the second generation fluoroquinolone, norfloxacin, was prepared and characterized (NOR-Zn complex, NZC). The antibacterial efficiency of the NZC was tested on two Gram-positive and four Gram-negative bacteria by minimum inhibitory concentration method. The cytotoxic potential of NZC on MDA (human breast adenocarcinoma), Caco-2 (human colon adenocarcinoma), and Hela (human cervix carcinoma) cell lines was studied. The DNA interaction property of the NZC has been investigated using UV-vis, fluorescence, Fourier transform infrared, as well as cyclic voltammetry methods. Intrinsic binding constant (K(b)), thermodynamic, and other spectroscopic and voltammetric data indicate that the NZC has more affinity for DNA than for norfloxacin and interacted with DNA via two modes: electrostatic and outside hydrogen binding. The proposed DNA binding mode supports the large enhancement in the cytotoxicity and antibacterial activity of NZC.

Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis

Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized β(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

Study of Cancer Cell Lines with Fourier Transform Infrared (FTIR)/ Vibrational Absorption (VA) Spectroscopy

In this work we have used Fourier transform infrared (FTIR) / vibrational absorption (VA) spectroscopy to study two cancer cell lines: the Henrietta Lacks (HeLa) human cervix carcinoma and 5637 human bladder carcinoma cell lines. Our goal is to experimentally investigate biochemical changes and differences in these cells lines utilizing FTIR spectroscopy. We have used the chemometrical and statistical method principal component analysis (PCA) to investigate the spectral differences. We have been able to identify certain bands in the spectra which are so-called biomarkers for two types of cell lines, three groups for the 5637 human bladder carcinoma cell line (5637A, 5637B and 5637C), and another one for the HeLa human cervix carcinoma cell line. The vibrational modes can be assigned to specific bands involving characteristic motions of the protein backbone. This work shows that infrared vibrational absorption (VA) spectroscopy can be used as a useful tool in medical diagnostics that provides in principle additional information and detail to that which can be obtained/provided from conventional histological studies, and more conventional mass spectroscopic and NMR techniques. The use of high level vibrational spectroscopic simulation, in addition to the chemometric and statistical tools of PCA, linear and quadratic discriminant analysis, and artificial networks methods that are good at finding correlations, but provide little if any physical, chemical and biochemical insight into the nature of the changes at a molecular level, is also strongly advocated and helpful to gain more physical, chemical and biological insight. Hence the combination of vibrational spectroscopic simulations and experimental vibrational absorption spectroscopy and imaging are advocated for future developments in this field.

Effect of an Isolated Active Compound (BVI03) of Boehmeria virgata (Forst) Guill leaves on Anti-Proliferation in Human Cancer Cervix HeLa Cells through Activation of Caspase 3 and p53 Protein

In this study, we found that BVI03 an alkaloid compound isolated from B. virgate induced antiproliferation against the human cervix carcinoma cell line HeLa. A MTT assay indicated that BVI03 had a strong tumor inhibition (IC50=0.126 μg/mL), which was superior to that of tamoxifen (IC50=2.879 μg/mL). This study also investigated the mechanism of antiproliferation induced by BVI03. Enzymatic activity using a colorimetric assay kit was performed to determine work mechanism of BVI03. Our data indicate that p53 and caspase-3 are involved in the process of BVI03-induced antiproliferative in HeLa cell compare with untreated HeLa cells.

Isolation, Biological Activity Evaluation, Structure Elucidation, and Total Synthesis of Eliamid: A Novel Complex I Inhibitor

Eliamid is a secondary metabolite isolated from two bacterial strains. This molecule features a linear polyketide backbone terminated by a tetramic acid amide moiety. Among other biological activities, eliamid shows a high and specific cytostatic action on human lymphoma and cervix carcinoma cell lines. The 2,4-anti relative configuration of the C-2,C-4-dimethyl substituted amide fragment was assigned by means of Breit's rule. The absolute configuration of all stereocenters was determined by a combination of degradation methods, structural similarity analysis and total synthesis. The stereogenic centers were introduced by vinylogous Mukaiyama aldol reaction and two consecutive Myers alkylations. The use of pentafluorophenyl ester as acylation agent allowed the efficient formation of tetramic acid amide. The longest linear sequence in the synthesis consist of 13 steps and proceeds with 12% overall yield. Differential spectroscopy experiments with beef heart submitochondrial particles established that eliamid is a potent inhibitor of the NADH-ubiquinone oxidoreductase complex. Additionally, biosynthesis of eliamid was investigated by feeding experiments with (13)C-labeled precursors.

Synthesis and anticancer activity of 5,6,8,13-tetrahydro-7H-naphtho[2,3-a][3]-benzazepine-8,13-diones

A series of naphthoquinones fused benzazepines, 5,6,8,13-tetrahydro-7H-naphtho[2,3-a][3]-benzazepine-8,13-diones, were synthesized and evaluated for their anticancer activity against four cell lines; human breast carcinoma cell line, human cervix carcinoma cell line, human hepatocellular carcinoma cell line and human keratinocyte cell line. The results showed that 5,6,8,13-tetrahydro-2,3,4,9-tetramethoxy-7H-naphtho[2,3-a][3]benzazepine-8,13-dione 4g and 5,6,8,13-tetrahydro-2,3,9-trimethoxy-7H-naphtho[2,3-a][3]benzazepine-8,13-dione 4h have significant cytotoxicity against a hepatocellular carcinoma cell line with IC(50) = 3.5 μg/mL and 3.0 μg/mL, respectively.