Cytotoxicity

The corrosion resistance of AISI 304 stainless steel (AISI 304 SS) and manganese stainless steel (low-nickel SS) brackets in artificial saliva was investigated. The cytotoxic effects of their corrosion products on L929 cell culture were compared by two assays, crystal violet, to evaluate cell viability, and MTT (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide), for cell metabolism and proliferation. The atomic absorption spectroscopic analysis of the corrosion products demonstrated that nickel and manganese ion concentrations were higher for the AISI 304 SS-bracket immersion solution as compared with the low-nickel SS brackets. Scanning electron microscopy and energy-dispersive spectroscopy demonstrated less corrosion resistance for the AISI 304 SS brackets. Although none of the bracket extracts altered L929 cell viability or morphology, the AISI 304 SS-bracket extracts decreased cellular metabolism slightly. The results indicated that the low-nickel SS presents better i...

. Miral 500 CS CASa 42509-80-8 , an organophosphorus insecticide, has been widely used in Colombia to fumigate coffee plantations. Therefore, there is extensive human exposure to this pesticide. Miral's mutagenic and genotoxic activities, however, are not known. In this study, such activities of the pesticide were evaluated using the Salmonella TA98rS9 test and the chromosome aberration assay in bone marrow cells of Swiss albino CD1 male mice. All doses tested Ž . with Salmonella in the presence of S9 mix 3.2, 16, 80, 400 and 2000 mgrplate induced a mutagenic response that was three times the spontaneous mutation frequency. The mutagenic response without S9 was twice the spontaneous frequency.

We herein describe the synthesis and characterization of nine new 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine. We evaluate their toxic effects against the different evolutive forms of Trypanosoma cruzi, and the host cell (murine macrophages). The results obtained show that mesoionic hydrochloride MI possesses the best activity profile. Compound MI may be a prototype for use in the development of a new chemotherapeutic agent with high efficiency, which may be employed in the treatment of Chagas' disease.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl) ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were ...

The use of copper-based alloys for fixed dental crowns and bridges is increasingly widespread in several countries. The aim of this work is to study the dissolution of a zinc-aluminum-bronze and the cytotoxic effects of the ions released on UMR-106 osteoblastic cell line. Two sources of ions were used: (1) ions released by the metal alloy immersed in the cell culture and (2) salts of the metal ions. Conventional electrochemical techniques, atomic absorption spectroscopy [to obtain the average concentration of ions (AC) in solution], and energy dispersive X-ray (EDX) spectroscopy analysis were used to study the corrosion process. Corrosion tests revealed a strong influence of the composition of the electrolyte medium and the immersion time on the electrochemical response. The cytotoxicity was evaluated with (a) individual ions, (b) combinations of two ions, and (c) the mixture of all the ions released by a metal disc of the alloy. Importantly, synergistic cytotoxic effects were found when Al-Zn ion combinations were used at concentration levels lower than the cytotoxic threshold values of the individual ions. Cytotoxic effects in cells in the vicinity of the metal disc were also found. These results were interpreted considering synergistic effects and a diffusion controlled mechanism that yields to concentration levels, in the metal surroundings, several times higher than the measured AC value. V

Aim. It is a very hot topic to investigate the effects and the mechanisms of action of biological active extracts such as thyme essential oil on various cancer cells. This paper examines the ability of thyme essential oil to inhibit the growth of DLD-1 colorectal cancer cells and if it is the case, determine the contribution of antioxidant effect to this ability. Methods. To do this, we treated human DLD-1 colorectal cancer cells with thyme essential oil and assessed its effects on cell proliferation by using real time cell analyzing system (Xcelligence System). Furthermore, we applied the same concentrations to the L929 fibroblast cells in order to determine if thyme essential oil has cytotoxicity on normal cells in the same concentrations it showed anticancer effects. Then, antioxidant ability of thyme essential oil was evaluated by using DPPH assay. Results. Thyme essential oil treated DLD-1 cells exhibited decreasing cell index values in a concentration-dependent manner. An inhibitor concentration 50 (IC 50) value of 0.347 mg/mL was achieved. On the other hand, when thyme essential oil was tested on L929 fibroblast cells, it was observed that thyme essential oil did not show cytotoxic effect on L929 fibroblast cells. IC 50 value was 22 mg/mL for this experiment. Besides, thyme essential oil showed a strong antioxidant effect on DPPH assay. Conclusion. When the antiproliferative and the antioxidant effects of thyme essential oil are considered, it can be concluded that thyme essential oil may be an alternative option in the treatment of colorectal cancer.

The mechanism of human tumor resistance to the antineoplastic drug bleomycin (BLM) is not known. We now provide evidence implicating metabolic inactivation in the resistance of human Burkitt's (Daudi) lymphoma to BLM. Daudi lymphoma and human head and neck squamous cell carcinoma (A-253) cells grown (s.c.) in nude mice were found to be resistant and sensitive to BLM treatment, respectively. Within l h of s.c. injection of (3H]BLM A2,Daudi xenografts accumulated less BLM and metabolized this drug to a much greater extent than did A-253 xenografts. The BLM-resistant Daudi xenografts metabolized BLM A2 to at least 6 metabolites and only a small proportion of the drug remained as unmetabolized BLM A2. In the BLM-sensitive A-253 xenografts, however, BLM A2 remained the major component. Incubation of BLM \; with Daudi cytosolic fractions resulted in a complex mixture of metabolites similar to that formed by Daudi xenografts in nude mice. This BLM metabolite mixture was biologically inactive in plasmili DNA degradation assays. Treatment of mice bearing Daudi xenografts with an inhibitor of BLM hydrolase, L-fra/w-epoxysuccinyl-leucylamido-(4guanidino)butane (E-64), prior to | 'I I|HI M A2 treatment did not affect the amount of BLM accumulated but inhibited BLM A2 metabolism in the xenografts. Furthermore, although E-64 alone did not inhibit the growth of Daudi xenografts, it potentiated the antitumor activity of BLM. These results indicate that Daudi tumors resist BLM by metabolically inactivating it and that inhibition of BLM metabolism in vivo enhances the antitumor activity of BLM and hence overcomes resistance.

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc 2 155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, a-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H 37 Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H 37 Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC 50) in the same order of magnitude (SI < 1). Interestingly the sesquiterpene alcohol a-prethapsenol was found to inhibit the growth of the pathogenic mycobacteria with an MIC value of 60 mg/L, being more specific towards mycobacteria than mammalian cells (SI~2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action.

AbstractÐThe vinyl phosphonate derivatives of uridine, cytidine, and cytosine arabinoside (ara-C) have been prepared through oxidation of appropriately protected nucleosides to the 5 H aldehydes and Wittig condensation with [(diethoxyphosphinyl)methylidine]triphenylphosphorane. Dihydroxylation of these vinyl phosphonates with an AD-mix reagent generated the new 5 H ,6 H -dihydroxy-6 H -phosphonates. After hydrolysis of the phosphonate esters and the various protecting groups, the six phosphonic acids were tested for their ability to serve as substrates for the enzyme nucleotide monophosphate kinase and for their toxicity to K562 cells.

Viper's venom is a source of biopharmaceutical compounds, hence the need to assess the effect of this animal extract on human blood. Here, we studied the blood coagulation disorders and hemolytic activities of the venom of M. bornmulleri viper. The pro-coagulant and anticoagulant effects are analyzed with venom concentrations ranging from 0.4 to 0.0031 mg/mL. Thus, the PT is way above the normal value indicating an anticoagulant activity whereas for the aPTT, the high concentration of the venom showed an anticoagulant activity, but a pro-coagulant effect was occurred when the venom concentration decreases to 0.05 and/or 0.025 mg/mL. Hemolytic tests, performed in suspension (30% RBCs) and on blood agar plate (5% RBCs), show that an increased concentration of the venom going until 1.6 mg cannot produce a hemolytic effect, even in the presence of Ca 2+ (hemolysis < 0.5%). Also, on the blood agar plate no hemolytic area appeared even with 0.04 mg of the lyophilized venom. Otherwise, the venom was able to induce a low hemolytic activity (hemolysis = 1.3 %) by acting on L-α-PC used as substrate. In this case, the destruction of erythrocytes increased proportionally to the added amount of phospholipids which are hydrolyzed to fatty acids and lysophospholipids (two toxic substances for RBCs), probably due to the presence of PLA2 in the venom and which are known by their ability to hydrolyze lecithin

A series of twenty 2,6-diarylpiperidin-4-one O-methyloximes were synthesized with fluoro/chloro/
bromo/methyl/methoxy/ethoxy/isopropyl substituents on various positions of the phenyl at C-2 and
C-6 in association with/without methyl substituent on the secondary amino group and methyl/ethyl/isopropyl
substituents on the active methylene centers. Regardless of their substitution all compounds predominantly
exist in the chair conformation except 3m, which adopts a twist-boat conformation. All the
synthesized compounds were evaluated for their in vitro antiproliferative activity against human cervical
carcinoma (HeLa) cell line. The cytotoxicity of the test compounds was determined by measuring the
number of live cells after 24 h of treatment by MTT assay method. This preliminary SAR suggests some
lead molecules 3c–f, 3j–k, 4d–g, and 4i with a scope of further structural optimization of the piperidone
pharmacophore toward the development of anticancer drug synthesis.

Palladium-based nanoparticles immobilized in polymeric matrices were applied to the reductive dechlorination of 3,3′,4,4′-tetrachlorobiphenyl (PCB77) at room temperature. Two different dechlorination platforms were evaluated using (1) Pd nanoparticles within conductive polypyrrole films; or (2) immobilized Fe/Pd nanoparticles within polyvinylidene fluoride microfiltration membranes. For the first approach, the polypyrrole film was electrochemically formed in the presence of perchlorate ions that were incorporated into the film to counterbalance the positive charges of the polypyrrole chain. The film was then incubated in a solution containing tetrachloropalladate ions, which were exchanged with the perchlorate ions within the film. During this exchange, reduction of tetrachloropalladate by polypyrrole occurred, which led to the formation of palladium nanoparticles within the film. For the second approach, the membranesupported Fe/Pd nanoparticles were prepared in three steps: polymerization of acrylic acid in polyvinylidene fluoride microfiltration membrane pores was followed by ion exchange of Fe 2+ , and then chemical reduction of the ferrous ions bound to the carboxylate groups. The membranesupported iron nanoparticles were then soaked in a solution of tetrachloropalladate resulting in the deposition of Pd on the Fe surface. The nanoparticles prepared by both approaches were employed in the dechlorination of PCB77. The presence of hydrogen was required when the monometallic Pd nanoparticles were employed. The results indicate the removal of chlorine atoms from PCB77, which led to the formation of lower chlorinated intermediates and ultimately biphenyl. Toxicity associated with vascular dysfunction by PCB77 and biphenyl was compared using cultured endothelial cells. The data strongly suggest that the dechlorination system used in this study markedly reduced the proinflammatory activity of PCB77, a persistent organic pollutant.

An examination of an organic extract of the cyanobacterium Lyngbya majuscula, collected from Wasini Island off the southern Kenyan coast, led to the isolation of the known cyclic depsipeptide antanapeptin A (1), recently isolated from a Madagascan collection of L. majuscula, and a new bioactive cyclic depsipeptide, homodolastatin 16 (2). The structures of these two compounds were determined from NMR and mass spectrometry data. Homodolastatin 16, a higher homologue of the potential anticancer agent dolastatin 16, exhibited moderate activity against oesophageal and cervical cancer cell lines. a 13 C NMR data for 5 acquired at 125 MHz; 1 H and 13 C NMR data for 2 acquired at 400 and 100 MHz, respectively. b Protons showing NOESY correlation with indicated proton(s). c Protons showing long-range correlation with indicated carbon.

Sjogren's syndrome (SS) is an exocrinopathy characterized by T cell infiltrates, salivary gland epithelial cell (SGEC) apoptosis and high Fas and FasL expression. To address the participation of T cell-derived cytokines and of Fas apoptotic pathway in SS glandular lesions, we utilized non-neoplastic SGEC lines established from SS patients and controls. Possibly attesting to their intrinsic activation, cell lines derived from SS patients displayed significantly higher constitutive Fas and FasL than controls. Surface co-expression of Fas and FasL was not associated with spontaneous fratricide apoptosis. SGEC were resistant to anti-Fas-mediated apoptosis (possibly owing to the constitutive expression of anti-apoptotic proteins cFLIP and Bcl-2), but became sensitive after protein or RNA synthesis inhibition. IFN-and TNF-were able to upregulate surface Fas and FasL, whereas IL-1 downregulated surface FasL. IFN-(but not several other cytokines) reduced the survival of SGEC in a dose-and time-dependent manner and induced Fas/FasL-mediated apoptosis, directly and via anoikia. Dexamethasone inhibited the upregulation of Fas and FasL by IFN-and the induction of SGEC apoptosis and detachment by anti-Fas mAb or IFN-. Our findings indicate the injurious role of IFN-for the salivary epithelia of SS patients through the induction of Fas-mediated apoptosis and anoikia.

A series of N-unsubstituted hydroxy-10H-acridin-9-ones were synthesized and evaluated for inhibitory action against HaCaT keratinocyte growth, in order to explore their potential as antipsoriatic agents. For structureeactivity relationship studies, the number and position of the hydroxyl groups were modified, the oxygen functions substituted or replaced, or additional functional groups were introduced into the acridone scaffold. 1,8-Dihydroxy-10H-acridin-9-one (4), which is an aza-analogue of the antipsoriatic anthralin, was only marginally active. However, 1,3-dihydroxy-substituted 5ee was the most potent acridone within this series and inhibited keratinocyte growth with an IC 50 value comparable to that of anthralin. In contrast to anthralin, nearly all members of the acridone series were devoid of radical generating properties, which were determined by their capability to interact with the free radical 2,2diphenyl-1-picrylhydrazyl. Structures with a phenolic hydroxyl or an aromatic amine arranged ortho or para to the acridone NH group were exceptions. Also in contrast to anthralin, membrane-damaging effects as documented by the release of lactate dehydrogenase into the culture medium were not observed for acridones.

Recent advances in nanotechnology led to the development of various nanostructures especially that of carbon-based nanomaterials (CBNs) for industrial and biomedical uses. As a result, the production as well as the human exposure to these materials will increase in the future. Thus, it is primordial to also know the associated health hazards. We performed in vitro cell viability studies on different types of cultured cells exposed to multiwalled carbon nanotubes and carbon nanoparticles. Our work indicates that the tested materials are toxic and that the effects of materials are cell type dependent. Light microscopic observations of the cells when exposed to the highest dose of nanomaterials showed morphological alterations, which are characteristic for cell death, and were most pronounced in the case of macrophage cells. Further experiments are aimed at elucidating the mechanisms of toxicity of CBNs.

In our continuing efforts to find new antiherpetic agents from plants, an extract prepared from the stems of Carissa spinarum L. was found to possess appreciable activity against herpes simplex viruses (HSV I and II). A chemical study of this plant was then initiated, and this led to the isolation of 12 compounds, including a coumarin, two cardiac glycosides and nine lignans. These isolated compounds were evaluated for several biological activities, including antiherpetic, cytotoxic, antioxidant and antibacterial effects. The cardiac glycoside evomonoside was found to be the only antiherpetic principle, showing moderate activity against herpes simplex virus types I and II in the inactivation method. The lignans (À)-carinol, (À)-carissanol and (À)-nortrachelogenin exhibited cytotoxicity against breast (MCF7) and lung (A549) cancer cells. Moderate anti-DPPH free radical activity was observed for all the lignans. None of the isolates showed antibacterial activity.

In our present study we investigated if the Monosodium glutamate (MSG) has any cytotoxic and genotoxic effect in animal system by studying cytogenetical parameters, namely chromosome aberration (CA), mitotic indices (MI) and sperm head anomaly (SHA) and a histo-pathological parameter i.e., tissue weight / body weight ratio in mice. Experiments were carried out at three different fixation intervals, namely, 7D, 14D and 21D, maintaining suitable controls. MSG was administered to mice at the dose 2 mg / gm of body weight. The investigation reveals that feeding of MSG induced geno-toxicity and cyto-toxicity. These produced greater amount of CA, SHA along with a general increase in the MI at significant levels. Thus, the increased level of genotoxicity and cytotoxicity could be attributed due to chronic feeding of the food additive MSG.

Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC 50 = 2.2 lM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 lg/ml, 258 lM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.

A congeneric series of novel imidazolone fused quinazolinone derivatives were synthesized and characterized by IR, NMR, mass spectra and elemental analyses. All the compounds were evaluated for their in vitro cytotoxic activity against cervical cancer (HeLa), breast cancer (MCF-7), leukemia cells (HL-60) and hepatocellular carcinoma (HepG2) cell lines. The derivative 4e which bears a methoxy group at para position in phenyl ring of imidazolone displayed three fold potent activity against MCF-7 than that of the standard drug Cisplatin. The IC 50 value of 4e against HepG2 is twofold lesser than Cisplatin whereas the IC 50 value against HeLa and HL-60 was equivalent to Cisplatin. The result concludes that these derivatives can be further utilized as a promising anticancer agent.

We have synthesized rigid analogues of combretastatin bearing a furan ring in place of the olefinic bridge. These compounds are cytotoxic at nanomolar concentrations in neuroblastoma cells, display a similar structure-activity relationship compared to combretastatin A4, and inhibit tubulin polymerization. We also show that the furan ring can be further functionalized. Thus, it is possible that combretafurans could act as scaffolds for the development of dual-action antitumoral agents.

Natural products play a major role in anticancer drug discovery as a unique source of original structures which can provide models for future drug design. Relevant examples currently used in the clinic include teniposide and etoposide derived from naturally occurring podophyllotoxin, taxotere based on the structure of the yew diterpene paclitaxel, topotecan and irinotecan developed from camptothecin, and semisynthetic vinca alkaloids such as vinorelbine and vinflunine originating from the lead structure vinblastine. 1) In this context, our group is interested in potential anticancer natural product-like compounds including an acridone or xanthone derived basic core and an additional fused dimethylpyran ring. Indeed, the fused dimethylpyran system, which arises in Nature from the condensation of a phenol with an active isoprene unit, appears as a privileged substructure present in numerous bioactive compounds exemplified by the insecticide chromenes precocenes, 2) the HIV-1 reverse transcriptase inhibitors calanolides, 3) and the antitumor acridone alkaloid acronycine (1). 4) Based on this latter model, we recently prepared the pentacyclic analogues benzo[a]acronycine (6methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one) (2) and and benzo[b]acronycine (6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one) (3), together with several series of corresponding 1,2-dihydrodiol diesters, which displayed significantly enhanced in vivo antitumor activity when compared to the parent alkaloid. 5-8) Such compounds are exemplified by cis-diacetate 4, developed under the code S23906-1, which is currently undergoing phase I clinical trials. 9) The mechanism of its action implies alkylation of the 2-amino group of DNA guanine residues by the carbocation resulting from the elimination of the ester leaving group at position 1 of the drug. 10-12) This mechanism is related to that implied in the cytotoxic and antitumor properties of the natural furanoxanthone psorospermine (5), isolated from Psorospermum febrifugum. 13-15) Actually, psorospermine has been shown to interact with DNA and to alkylate the N-7 of the guanine residues. 16,17) In a continuation of our studies on the structure activity relationships in the acronycine series, 18-24) we describe here the synthesis and biological activites of

The antibacterial and anticollagenolytic properties of tetracycline (TCN) are valuable in periodontal therapy, and TCN treatment can remove the smear layer following root instrumentation. However, recent reports pointing to cytotoxic effects of several acids prompted this study to define TCN concentrations that are anticollagenolytic and remove the smear layer, but have low cytotoxicity.

The chemical composition of essential oils of six Stachys species, S. cretica L. ssp. vacillans Rech. fil., S. germanica L., S. hydrophila Boiss., S. nivea Labill., S. palustris L. and S. spinosa L., obtained by hydrodistillation, was studied by GC and GC–MS. All the oils have in common a great percentage of fatty acids and esters (24.2–58.5%) and a high

Four new sesquiterpenes, chlorajapolides F-I (1-4), along with nine known terpenoids (5-13) were isolated from the aerial part of Chloranthus japonicus. Their structures were elucidated on the basis of spectroscopic analysis, and a lindenane sesquiterpene, named 9-hydroxy-heterogorgiolide, previously isolated from the C. japonicus, was revised as its 8-epimer (1a). Moreover, methanol extract (ME), EtOAc fraction (EF), water fraction (WF), and all isolates (1a, 1-13) were evaluated for their cytotoxicities using two human cancer cell lines.

Depression is a public disorder worldwide. Despite the widespread use of venlafaxine in the treatment of depression, it has been associated with the incidence of toxicities. Hence, the goal of the current investigation was to evaluate the mechanisms of venlafaxine–induced cell death in the model of the freshly isolated rat hepatocytes. Methods: Collagenase-perfused rat hepatocytes were treated with venlafaxine and other agents. Cell damage, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential decline, lysosomal damage, glutathione (GSH) level were analyzed. Moreover, rat liver mitochondria were isolated through differential centrifugation to assess respiratory chain functionality. Results: Our results demonstrated that venlafaxine could induce ROS formation followed by lipid peroxidation, cellular GSH content depletion, elevated GSSG level, loss of lysosmal membrane integrity, MMP collapse and finally cell death in a concentration-dependent manner. N-acetyl cysteine, taurine and quercetine significantly decreased the aforementioned venlafaxine-induced cellular events. Also, radical scavenger (butylatedhydroxytoluene and α-tocopherol), CYP2E1 inhibitor (4-methylpyrazole), lysosomotropic agents (methylamine and chloroquine), ATP generators (L-gluthamine and fructose) and mitochondrial pore sealing agents (trifluoperazine and L-carnitine) considerably reduced cytotoxicity, ROS generation and lysosomal leakage following venlafaxine treatment. Mitochondrion dysfunction was concomitant with the blockade of the electron transfer complexes II and IV of the mitochondrial respiratory system. Conclusion: Therefore, our data indicate that venlafaxine induces oxidative stress towards hepatocytes and our findings provide evidence to propose that mitochondria and lysosomes are of the primary targets in venlafaxine-mediated cell damage

Two new compounds, a cyclic peptide desmocyclopeptide (1) and a special flavone desmorostratone were isolated from the stem bark of Desmos rostrata, along with two known compounds, desmosdumotins B (3) and C (4). Their structures were established on the basis of the spectral data, including mass spectrometry and 2D NMR. The total synthesis of desmorostratone (2) was performed in order to confirm its structure as well as that of desmosdumotin C (4), which was a tautomeric mixture in the solution. Finally, cytotoxity of these compounds were evaluated. Desmosdumotin C (4) displayed a moderate inhibition activity against KB cell line with an IC 50 of 19.2 mM, whereas the other products showed a weak inhibition against the same cell line target. Tetrahedron j o u r n a l h o m e p a g e : w w w . e l s e v i e r. c om / l oc a t e / t e t molecular formula itself and from elucidation of its NMR spectra. Analysis of the 1 H and 13 C NMR spectral data for 1, with the aid of 1 H-1 H-COSY, HSQC, HMBC and NOESY spectra, indicated the presence of an alanine, a glycine, a proline, an isoleucine and a phenylalanine ). The determination of the peptide sequence was established from the connectivity of the carbonyl of residue (i) and the NH proton of residue (iþ1) on the HMBC spectrum as follows: the correlations of the carbonyl at d C 173.5 of the Ala 1 with its Ha proton at d H 4.37, as well as to the NH proton of the Gly 2 at d H 7.78 were observed. The carbonyl group of the Gly 2 at d C 168.5 was not correlated to an amide proton, suggesting its connection with the Pro 3 . Cross-peaks of the carbonyl of the Pro 3 at d C 172.1 with its Ha proton at d H 4.21 and NH proton (d H 7.12) of the Ile 4 were presented. In addition, the carbonyl of Ile 4 at d C 172.3 was correlated with its Ha proton at d H 4.18 and NH proton of Phe 5 at d H 7.56. Finally, 2 J-HMBC correlation of the carbonyl of Phe 5 at d C 172.3 with its Ha proton (d H 4.64) and NH proton of Ala 1 (d H 8.25) were noted. Complete analysis of the HMBC spectrum determined the structure of 1 as drawn in . The NOESY spectrum of 1 depicted the strong spatial interactions of Ha of Gly 2 with Hd of Pro 3 , indicating that the amide bond between Gly 2 -Pro 3 was trans. 4 The d NN(i,iþ1) and d aN(i,iþ1) sequential connectivity from Ala 1 to Phe 5 was clearly observed in the NOESY spectrum as indicated in . The amino acids residue and the sequence of 1 were confirmed by fragmentation of [MþH] þ ion at m/z 486. A series of adjacent a n ion peaks were observed at m/z 311, 240, 183 and 86 corresponding to the successive loss of Phe, Ala, Gly and Pro. A second series of peaks at m/z 339, 268, 211 and 114 were assigned to adjacent b n ion (loss of Phe, Ala, Gly and Pro). This new pentacyclopeptide 1 is named desmocyclopeptide. The structure of 1 is very close to that of pseudostellarin A which has been previously reported from the roots of Pseudostellaria heterophylla. 5

Complexes of the type trans-[PdX 2 (isn) 2 ] {X ¼ Cl (1), N 3 (2), SCN (3), NCO (4); isn ¼ isonicotinamide} were synthesized and evaluated for in vitro antimycobacterial and antitumor activities. The coordination mode of the isonicotinamide and the pseudohalide ligands was inferred by IR spectroscopy. Single crystal X-ray diffraction determination on 2 showed that coordination geometry around Pd(II) is nearly square planar, with the ligands in a trans configuration. All the compounds demonstrated better in vitro activity against Mycobacterium tuberculosis than isonicotinamide and pyrazinamide. Among the complexes, compound 2 was found to be the most active with MIC of 35.89 mM. Complexes 1e4 were also screened for their in vitro antitumor activity towards LM3 and LP07 murine cancer cell lines.

In this study, the cytotoxicity of medical latex gloves to cultured L-929 cells was determined using various extraction conditions. According to the extraction time and temperature, three types of extraction conditions were used: 1) 24 h at 37 ; 2) 72 h at 37 ; 3) 72 h at 50 . Also, four different extraction vehicles were used, namely, distilled water (DW), 9 g/l sodium chloride (saline) in DW, and culture media with or without serum. Under the above-mentioned conditions, the samples were extracted and then 2-fold serially diluted in the concentration range 3.13 -50%. When extracted with either DW or saline for 24 h or 72 h at 37 , only 50% diluted samples showed distinct cytotoxicity to L-929 cells. Moreover, no cytotoxic potentials were observed when gloves were extracted with DW or saline at 50 for 72 h. Cytotoxicity was markedly greater when gloves were extracted with culture medium, irrespective of the presence of serum in the medium. These results suggest that optimal extraction conditions should be established for the cytotoxicity evaluations of biomaterials and medical devices.

A new cardenolide glycoside, vallarisoside (1), and a known one, 3β-O- (α-acofriosyl)-16-anhydrogitoxigenin (2) along with a new glycoside, benzyl 2-O-β-apiofuranosyl-(1→2)-β-D-glucopyranosyl-2, 6-dihydroxybenzoate (3) were isolated from Vallaris solanaceae. Structures of the isolates were elucidated by 1D and 2D NMR and mass spectroscopic analysis.  Of the isolates, vallarisoside (1) showed potent TRAIL-resistance-overcoming activity in human gastric adenocarcinoma (AGS) cells and cell-growth-inhibitory activity against HeLa and SW480 cells.

Background: Enterococcus faecalis is one of the bacteria that commonly found in root canal and pulp infection after root canal treatment. Sodium hypochlorite is the most widely used root canal irrigation, but it has toxic properties if exposed to periradicular tissues. It is necessary to develop an alternative for root canal irrigation. Fig leaf (Ficus carica Linn.) extract contains active substances such as flavonoid, tannin, and terpenoid which have been known for their antibacterial potency. Aim: This study aimed to determine the minimum bactericidal concentration (MBC) of fig leaf (F. carica Linn.) extract against E. faecalis and its cytotoxicity on fibroblast cells in vitro. Materials and Methods: A serial dilution method was used to determine the MBC of fig leaf extract on E. faecalis which grown on nutrient agar media. Inoculation was carried out at concentrations that suspected minimum inhibitory concentration (MIC), MBC, concentration between MIC and MBC, and control groups...

Bioassay-directed fractionation of the dried roots of Asparagus cochinchinensis led to the isolation of a new spirostanol saponin, asparacoside (1), two new C-27 spirosteroids, asparacosins A (2) and B (3), a new acetylenic derivative, 3′′-methoxyasparenydiol (4), and a new polyphenol, 3′-hydroxy-4′-methoxy-4′dehydroxynyasol (6), as well as five known phenolic compounds, asparenydiol (5), nyasol (7), 3′′methoxynyasol (8), 1,3-bis-di-p-hydroxyphenyl-4-penten-1-one (9), and trans-coniferyl alcohol (10). Compounds 1, 6, and 8 demonstrated moderate cytotoxicities in a panel comprised of KB, Col-2, LNCaP, Lu-1, and HUVEC cells, with IC 50 values ranging from 4 to 12 µg/mL. The structures were determined by spectroscopic and chemical methods.

In the literature, the anticancer potential of flurbiprofen isn't fully understood. In this study, the cytotoxic, genotoxic, and apoptotic effects of flurbiprofen were evaluated in human cervical and liver cancer cells. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and it was observed that cytotoxicity increased in a concentration-and time-dependent manner. Genotoxicity was determined using alkaline Comet assay. DNA damage increased in a concentration-dependent manner. Early apoptosis was evaluated using real-time polymerase chain reaction, and it was found that apoptotic gene levels increased while antiapoptotic gene levels decreased. Late apoptosis and cell cycle analyzes were determined using flow cytometry. No evidence of late apoptosis was observed, and no significant arrest was found in the cell cycle. In conclusion, it seems that flurbiprofen has a cytotoxic, genotoxic, and apoptotic effects in both human cancer cell lines. Moreover, the findings indicate that flurbiprofen is effective at the gene level and induces apoptosis with an intracellular pathway.

A series of 3,4-dihydro-2H-benzo[e]-, 2,3-dihydro-1H-naphtho[1,2-e]-, 3,4-dihydro-2H-naphtho[2,1e][1,3]oxazine and 1,2-bis(3,4-dihydrobenzo[e][1,3]oxazin-3(4H)-yl)ethane derivatives was obtained through an eco-friendly Mannich type condensation-cyclization reaction of phenols or naphthols with formaldehyde and primary amines in water at ambient temperature. Preliminary in vitro antimicrobial activity of the synthesized compounds was assessed against six pathogenic fungi, two Gram-negative and two Gram-positive bacteria. Some of the screened compounds have shown significant in vitro antimicrobial effect. Cytotoxic activities of the lead compounds (2m, 2n, 3c and 3d) against mouse fibroblast cell line (L929) were determined by MTT method. The assay results revealed that these molecules offered remarkable viability (>90%) of L929 cells at concentration of 25 mg/mL.