Cytotoxic effects of tris(2,3-dibromopropyl)phosphate and 2,4-diaminoanisole.

The flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) and the hair-dye component 2,4-diaminoanisole (2,4-DAA) were studied by possible cytotoxic effects in rat hepatoma cells grown in culture and in suspensions of isolated rat hepatocytes. Cell growth of Reuber cells was inhibited by 50% at 50 microgram/ml Tris-BP and 20 microgram/ml 2,4-DAA, respectively. At 200 microgram/ml Tris-BP protein synthesis in Reuber cells was reduced by 40%, whereas 50% inhibition of protein synthesis in isolated hepatocytes was seen at 100 microgram/ml. IC50 of 2,4-DAA with respect to protein synthesis was found at 400 microgram/ml in Reuber cells and at 3600 microgram/ml in MH1C1 cells, whereas in the isolated hepatocytes IC50 was 650 microgram/ml. DNA synthesis was inhibited by 50% at 225 microgram/ml Tris-BP in Reuber cells. At 500 microgram/ml 2,4-DAA DNA synthesis in Reuber and MH1C1 cells was inhibited by more than 80%.     

Metabolic activation of 2,4-diaminoanisole, a hair-dye component--II. Role of cytochrome P-450 metabolism in irreversible binding in vitro.

Incubation of rat liver microsomes with radiolabeled 2,4-diaminoanisole (2,4-DAA) in the presence of NADPH and oxygen led to the formation of irreversibly bound products to microsomal protein. The binding was inhibited by a CO:O₂ atmosphere and by an antibody against NADPH cytochrome c reductase. In vivo and in vitro inhibitors of cytochrome P-450 decreased the binding and phenobarbital-pretreatment increased binding, whereas β-napthoflavone-pretreatment was without effect. Binding of ring-labeled 2,4-DAA was much higher than with methyl-labeled-2,4-DAA. Experiments with [³H]-ring-and [¹⁴C]-ring-labeled-2,4-DAA indicated some loss of tritium; this was confirmed by isolation of labile tritium. Substitution of the hydrogens in the methyl group with deuterium led to increases in both binding and mutagenicity of 2,4-DAA. Formation of formaldehyde and a small amount of methanol could be demonstrated during the oxidative metabolism of methyl-labeled-2,4-DAA. Addition of superoxide dismutase and ascorbic acid inhibited binding, and a small amount of irreversible binding could be demonstrated when NADPH was replaced by a xanthine-xanthine oxidase system. Microsomes from rat kidneys also activated 2.4-DAA in the presence of NADPH. Thin-layer chromatography revealed that 30–40 per cent of 2.4-DAA was oxidized during 10 min of incubation with liver microsomes. And a tentative scheme involving aromatic hydroxylation, oxidative demethylation and N-hydroxylation for the microsomal metabolism of 2,4-DAA is presented. Irreversible binding could also be shown with liver microsomal RNA in vitro, whereas no binding to exogenously added DNA could be found.     

9-Deazaadenosine—A new potent antitumor agent

9-Deazaadenosine (9-DAA), a novel purine analog, was found to be a potent inhibitor of the growth of nine different human solid tumor cell lines in vitro and of pancreatic carcinoma (DAN) in antithymocyte serum (ATS)-immunosuppressed mice. In culture, ic₅₀ values ranged from 1.1 to 8.5 × 10^?8 M. Ovarian carcinoma (MR) was the only cell line in which the activity of 9-DAA was potentiated (about 10-fold) by pretreatment with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF). After incubation of cultured pancreatic DAN cells with 9-DAA (10-^?5M) for 2 hr, a peak appeared in the triphosphate region of HPLC nucleotide profiles that was identified tentatively as 9-deazaATP. Under the same incubation conditions, the incorporation of [³H]uridine into RNA and of [³H]thymidine into DNA was inhibited by 34 and 80% respectively. In vivo studies using ATS-immunosuppressed mice showed that 9-DAA at 0.4 mg/kg/day for 3 consecutive days reduced pancreatic carcinoma (DAN) tumor weights to approximately 50% of untreated controls. The nucleoside transport inhibitor p-nitrobenzyl-6-thioinosine (NBMPR) was shown to selectively protect host tissues from 9-DAA toxicity and, thereby, potentiated the antitumor activity of 9-DAA in vivo at optimal dosages.     

Recombinant high-density lipoprotein complex as a targeting system of nosiheptide to liver cells

Nosiheptide is a lipophilic peptide of significant anti-hepatitis B virus (anti-HBV) activity in cell culture, but has poor distribution to liver in vivo. In this study, recombinant high-density lipoprotein (rHDL) complexes of nosiheptide were constructed to target this anti-HBV agent to hepatocytes. The optimized rHDL–nosiheptide complex had a high drug-loading efficiency (>80%) and a diameter smaller than 30 nm. The concentration of nosiheptide in an optimized rHDL–nosiheptide complex to achieve 50% virus inhibition (IC₅₀) in HepG₂ 2.2.15 cells was 0.63 μg/ml, which was 40 times lower than the IC₅₀ of nosiheptide in control liposome (2.5 μg/ml) and 200 times lower than the IC₅₀ of the free nosiheptide (12.5 μg/ml). The complex targeted most of the administered nosiheptide to the liver within 30 min after i.v. injection to male Wistar rats. Together, this report provides early evidence that it is feasible to develop efficient, HDL-based drug delivery systems against HBV, utilizing apolipoprotein A-I as the targeting moiety.     

Novel pyrazole derivatives as anticancer and radiosensitizing agents

The present article describes the synthesis of some novel pyrrole, pyrazolo[4,3-d]oxazole, pyrrolo[2,3-b]pyridine, 1,2,3-triazole and oxoazetidin derivatives incorporating pyrazole moiety, the structures of which were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in-vitro antitumor activity against liver and colon human tumor cell lines (HEPG2 and HCT), furthermore, the most potent compounds were evaluated for their ability to enhance the cell killing effect of γ-radiation (radiosensitizing evaluation). The results of in-vitro anticancer evaluation showed that compounds 3 and 16a were the most potent compounds on HEPG2 (IC50=2.6 and 4.2 μg/ml) and compounds 2 and 10 were the most potent on HCT (IC50=2.7 and 3.9 μg/ml) compared to vinblastine (IC50=4.6 on HEPG2 and 2.6 μg/ml on HCT), while, the activity of the most potent compounds increased after combination with γ-radiation and they showed no toxicity on normal hepatocytes and colon cells at their effective concentrations.     

Nicotine-induced depression of lymphocyte growth

Because of the suspected action of lung irritants on pulmonary defense mechanisms, studies were performed in vitro to assess the potential toxicity of vanadium oxides on rabbit alveolar macrophages. Alveolar macrophages obtained by lung lavage and maintained in supplemented Medium 199 were exposed to particulate forms of vanadium pentoxide (V₂O₅), vanadium trioxide (V₂O₃), or vanadium dioxide (VO₂). Cell viability after a 20-hr exposure was reduced by 50% at approximately 13 μg V/ml as V₂O₅, 21 μg V/ml as V₂O₃, and 33 μg V/ml as VO₂. Cytotoxicity was determined to be directly related to solubility in the order V₂O₅ > V₂O₃ > VO₂. When V₂O₅ was dissolved in media prior to exposure of cells, only about 9 μg V/ml was required to reduce viability by 50% and to decrease total cell numbers by 70% in 20 hr as compared to control cultures. Dissolved V₂O₅ at 6 μg V/ml also reduced phagocytosis of polystyrene-latex spheres by about 50% as compared to controls after 20 hr. Exposure of cells or cell-free sonicates to dissolved V₂O₅ at concentrations as high as 50 μg V/ml produced only small changes in the specific activities of lysozyme or β-glucuronidase. However, acid phosphatase in the cell-free system was 70% inhibited by dissolved V₂O₅ at 1 μg V/ml. These findings suggest that exposure to vanadium oxides may alter alveolar macrophage integrity and function to the detriment of pulmonary defense.     

Synthesis of RNA in the pineal gland during N-acetyltransferase induction. The effects of actinomycin D, alpha-amanitin and cordycepin.

The biosynthesis of poly(A) containing RNA in the cultured rat pineal was monitored during the isoproterenol-induced increase in N-acetyltransferase activity in the presence of various inhibitors of RNA synthesis. The induction of N-acetyltransferase in the pineal gland by the β-agonist isoproterenol was found to be inhibited by actinomycin D and α-amanitin, but relatively insensitive to cordycepin. The concentration of actinomycin D which inhibits the induction process 50 per cent is on the order of 5 μg/ml, whereas only 0.1 μg/ml is needed to inhibit poly(A)-containing RNA synthesis by 50 per cent. Cordycepin, which inhibits the addition of poly(A) into newly synthesized messenger RNA, inhibited poly(A)-containing RNA synthesis by 85 per cent but inhibited the induction of N-acetyltransferase by isoproterenol only 15 per cent. The mushroom toxin a-amanitin, which should preferentially inhibit messenger type RNA synthesis, reduced poly(A)-containing RNA synthesis 50 per cent at 10 μg/ml of toxin, and inhibited enzyme induction 50 per cent at 40 μg/ml. While these results support the participation of an RNA species in the apparent induction of N-acetyltransferase in the pineal gland, they suggest that the induction stimulus may not be exerting its effect by simply causing an increase in the synthesis of messenger RNA containing a poly(A) terminus.     

Antitumor activity of arylacetylshikonin analogues

Twenty one phenylacetylshikonin analogues were synthesized from various substituted phenyl acetic acids and their cytotoxicity values against A549, K562 and L1210 cell lines and antitumor action in mice bearing S-180 cells were measured. All of phenylacetylshikonin analogues expressed a potent cytotoxicity (ED₅₀, 0.1–1.80 μg/ml) against L1210 and K562 cells. L 1210 cells were the most sensitive to shikonin analogues among these cells. Except 4-methoxyphenylacetylshikonin (0.098μg/ml) and α-acetoxyphenylacetylshikonin (0.10μg/ml), all other shikonin derivatives showed higher ED₅₀ values than phenylacetylshikonin (0.13μg/ml) in L 1210. In K562 cell, α-substitution of phenylacetylshikonin (0.1 μg/ml), while other substitutions increased it slightly; 4-methoxyphenylacetylshikonin (0.033 μg/ml) showed a exceptionally good cytotoxicity against K562 cell. 4-Halogenation tended to decrease the cytotoxic effect on L1210 cells, while it enhanced the effect on K562; 4-bromophenylacetyl [ED₅₀ (L1210)=1.76 μ/ml, ED₅₀ (K 562)=0.32 μg/ml] and 4-chlorophenylacetyl shikonin [ED₅₀ (L 1210)=1.64 μg/ml, ED₅₀ (K562)=0.32 μg/ml]. In contrast, A549 cells were much less sensitive to these shikonin analogues which showed ED₅₀ values of 1.5–13.5 μg/ml. Most of phenylacetylshikonin derivatives showed good antitumor activity in mice bearing S-180 cells. α-A-cetoxyphenylacetylshikonin and 4-dimethylaminophenylacetylshikonin showed highest T/C value (192–195%), implying that introduction of α-acetyl or of 4-dimethyl amino group gave a positive effect on the antitumor activity. Introduction of 4-dimethylamino group enhanced the antitumor activity as shown for 4-dimethylaminophenylacetylshikonin (T/C, 192%). It might be due to improvement of water solubility by dimethylamino group in the molecule.     

Biochemical effects of d-tetrandrine and thalicarpine.

The benzylisoquinoline alkaloids d-tetrandrine and thalicarpine inhibit the biosynthesis of DNA, RNA and proteins, when incubated with S180 cells in vitro. Oxidation of glucose[¹⁴C] to ¹⁴CO₂ was not affected by either alkaloid at levels up to 100 μg/ml in vitro. Incorporation of labeled acetate into lipids was inhibited only by thalicarpine at 100 μg/ml. Inhibition of the incorporation of thymidine into DNA was also observed in vivo after treatment with these drugs at 30–120 mg/kg; under these conditions, the synthesis of RNA and protein was not inhibited. In an attempt to elucidate the mechanism for inhibition of nucleic acid synthesis, the interaction of DNA, RNA and polynucleotides with the alkaloids was studied by gel filtration and dialysis. The two drugs associated with both DNA and RNA, but exhibited different affinities for the five polynucleotides examined. Both alkaloids were bound by polyguanylic and polyadenylic acids, but whereas d-tetrandrine associated only poorly with polythymidylic acid and not at all with polyuridylic acid, it was polycytidylic acid that showed no affinity for thalicarpine.     

Arsthinol nanosuspensions: pharmacokinetics and anti‐leukaemic activity on NB4 promyelocytic leukaemia cells

Objectives The organoarsenical arsthinol was used in the 1950s in the treatment of amoebiasis and yaws and was considered as ‘highly tolerated’. The aim of this work was to study its anti‐leukaemic activity and to develop nanosuspensions of the drug, thereby limiting brain concentrations and the risk of encephalopathy. Methods Arsthinol nanosuspensions were produced by high‐pressure homogenization. The anti‐leukaemic activity was assessed on NB4 acute promyelocytic leukaemia cells (vs solutions of arsthinol, As₂O₃ and melarsoprol). In addition, a pharmacokinetics study was performed to compare the nanosuspensions and the solution of arsthinol. Key findings Arsthinol induced growth inhibition of NB4 cells at lower concentration (IC50 (concentration inhibiting growth by 50%) = 0.78 ± 0.08 μmol/l after 24 h) than As₂O₃ (IC50 = 1.60 ± 0.23 μmol/l after 24 h) or melarsoprol (IC50 = 1.44 ± 0.08 μmol/l after 24 h). When formulated as nanosuspension, arsthinol remained cytotoxic (IC50 = 1.33 ± 0.30 μmol/l after 24 h). This formulation also reduced the drug's access to the brain (C_max = 0.03 μmol/g) whereas bone marrow concentrations remained very high (C_max = 2 μmol/g). Conclusions Nanosuspensions of arsthinol could be proposed for further studies in the treatment of acute promyelocytic leukaemia.     

Effect of actinomycin D on uptake and incorporation of thymidine and hypoxanthine into the acid-soluble and acid-insoluble fractions of rat hepatoma cells grown in culture

Preincubation of MH₁C₁, rat hepatoma cell cultures with actinomycin D between 0.01 μm/ml and 10.0 μm/ml gives a dose-dependent increase in the uptake of thymidine into the acid-soluble fraction up to 400 per cent of controls; the same increase is found in the acid-insoluble fraction. The effect is detectable after 5 min incubation, but is only fully developed after 1–2 hr treatment with the drug. The stimulation could not be blocked by cycloheximide. Preincubation with actinomycin D has little effect on uridine uptake compared to that of thymidine; actinomycin D 1.0 μm/ml after 2 hr increases uridine uptake to 131 per cent of controls. In contrast the uptake of hypoxanthine is inhibited by actinomycin D, 50 per cent inhibition is seen at 0.75 μm/ml. The apparent K_m for the thymidine uptake is 5.9 × 10^?6 M; actinomycin D pretreatment altered the V_max of the reaction but did not change the apparent K_m. The apparent K_m for the hypoxanthine uptake is 5.0 × 10^?6 M; actinomycin D pretreatment gave an apparently noncompetitive inhibition. Actinomycin D does not change the activity of thymidine kinase in homogenates of the cells.     

Observations on the 2,4-Dichlorophenoxyacetic Acid (2,4-D) Excretion in the Goat

Abstract The protein binding of 2,4-D in goat plasma was studied by means of equilibrium dialysis and the renal excretion of 2,4-D in three female goats by means of clearance methods. At low plasma levels of 2,4-D (<20 μg/ml) about 97 per cent of 2,4-D is bound to plasma proteins. The fraction of 2,4-D bound to plasma proteins decreases with rising plasma 2,4-D concentrations. A tubular secretion mechanism for 2,4-D, with a T_m value of about 9 mg (40μmol)/min., is demonstrated. The contribution from the tubules to the 2,4-D excreted per minute is greater than 97 per cent at a plasma 2,4-D level of 10 μg/ml. At moderate and high plasma 2,4-D concentrations (>40 μg/ml) the inulin clearance decreases with rising plasma 2,4-D concentrations.     

Inhibition of 15-Hydroxyprostaglandin Dehydrogenase Activity in Rabbit Gastric Antral Mucosa by Panaxynol Isolated from Oriental Medicines

Panaxynol is a polyacetylene compound with anti-inflammatory and anti-platelet-aggregatory effects isolated from commonly used oriental medicines. The effects of panaxynol on the activity of prostaglandin-synthesizing and catabolizing enzymes in the rabbit gastric antral mucosa have been examined. At concentrations ranging from 25 to 200 μM panaxynol had no effect on the synthesis of prostaglandins E₂, F₂α and D₂ from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa whereas at 25–200 μM it dose-dependently inhibited the activity of 15-hydroxyprostaglandin dehydrogenase (PGDH), which catalyses the initial step of prostaglandin catabolism, in the cytosolic fraction. The concentration required for 50% inhibition (IC50) was approximately 25 μM. Inhibition of PGDH by panaxynol was non-competitive with regard to NAD+ and prostaglandin E₂. These results suggest that panaxynol has the potential to inhibit PGDH activity in gastric mucosa, possibly as a result of pharmacological activity.     

7β-羟基胆固醇-3,7-双琥珀酸单酯钠(RS034)对 Ehrlich 腹水癌细胞DNA、RNA及蛋白质合成的影响

以同位素体外掺入方法研究了7β-羟基胆固醇-3,7-双琥珀酸单酯钠(RS034)对小鼠 Ehrlich 腹水癌细胞 DNA、RNA 及蛋白质合成的影响。加药50μg/ml 和5μg/ml 后半小时,即对 DNA 合成产生显著的抑制作用,抑制率分别达到66.8%和52.9%;50μg/ml 剂量组对 RNA 合成也有显著的抑制作用;但上述两个剂量对蛋白质合成不仅无抑制作用,相反能显著地促进合成。RS034对肿瘤细胞核酸合成的抑制作用可能是其抗癌作用机制之一。     

In vitro activities of LB20304, a new fluoroquinolone

Thein vitro activity of LB20304 was evaluated against clinical isolates and compared with those of Q-35, ciprofloxacin, sparfloxacin, lomefloxacin and ofloxacin. LB20304 demonstrated 16- to 64-fold more potent activity than ciprofloxacin against gram-positive bacteria. LB20304 inhibited 90% of the isolates of methicillin-susceptibleStaphylococcus aureus (MSSA) at a concentration of 0.016 μg/ml (MIC₉₀). MIC₉₀ values of LB20304 against methicillin-resistantStaphylococcus aureus (MRSA), methicillin-susceptibleStaphylococcus epidermidis (MSSE), methicillin-resistantS. epidermidis (MRSE) andStreptococcus pneumoniae were 2 μg/ml, 0.016 μg/ml, 0.5 μg/ml and 0.031 μg/ml, respectively. LB20304 was also very active against gram-negative bacteria. AgainstEscherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa andAcinetobacter calcoaceticus, MIC₉₀S of LB20304 were 0.031 μg/ml, 0.25 μg/ml, 2 μg/ml, 8 μg/ml and 0.5 μg/ml, respectively. Its activity was comparable to that of ciprofloxacin but much better than those of Q-35, sparfloxacin, ofloxacin and lomefloxacin. LB20304 also exhibited the most potent activity among quinolones tested against laboratory standard strains, ofloxacin-resistant strains, β-lactamase-producing strains and anaerobic strains. The inhibitory effect (IC₅₀) of LB20304 on DNA gyrase fromMicrococcus luteus, determined by the supercoiling assay, was 8-fold more potent than that of ciprofloxacin. LB20304 did not induce topoisomerase-associated DNA cleavage even at a concentration of 10 mg/ml, although ciprofloxacin induced DNA cleavage at a concentration of 1 mg/ml.     

Antimitochondrial activity of lampren in Saccharomyces cerevisiae

Twenty-four haploid strains of Saccharomyces cerevisiaewere totally inhibited in growth in the presence of 0.5 μg/ml Lampren in conditions of obligatory mitochondrial function. In a fermentable medium on the other hand, 10 μg/ml of the drug permitted growth but with extended lag period. The drug stimulated oxygen uptake 2- to 3-fold when added to respiring cells and to rat liver mitochondria respectively, and restored oxygen uptake in cyanide-inhibited cells by about 35 per cent. It was concluded that Lampren acts as a hydrogen acceptor using substrates of the respiratory chain and by-passing cytochrome oxidase. Supporting evidence was seen in a correlation between Lampren and phenazine methosulphate which is chemically related to the drug.Yeast strains and their Lampren-resistant mutants showed a good cross-resistance relationship with oligomycin, triethyl tin and chlorimipramine, known inhibitors of mitochondrial function. The antimitochondrial action of Lampren (the first to be reported) results in depressed protein and RNA synthesis in cells metabolizing glycerol at low concentrations of the drug (about 5 μg/ml inhibits 50 per cent biosyn-thesis in a sensitive strain), but 20 μg/ml are required to inhibit these processes to a significant degree in a glucose medium.     

Antitrypanosomal and cytotoxic activities of pyrrolizidine alkaloid‐producing plants of Ethiopia

Objectives The objective was to determine the in‐vitro effect of extracts from 19 Ethiopian plant species and four pure pyrrolizidine alkaloids on bloodstream forms of Trypanosoma brucei brucei and human leukaemia HL‐60 cells. Methods Crude plant extracts were prepared using methanol and dichloromethane. The alkaloidal extracts from Solanecio angulatus flowers were prepared with and without zinc reduction using the acid‐base extraction method. Cell proliferation inhibitory activity of the extracts and compounds was assessed using Alamarblue. Key findings The most active extract was the dichloromethane extract of Solanecio angulatus flowers, with an IC50 value of 12.17 μg/ml. The best selectivity index (SI > 41.08) was obtained for the same extract determined with HL‐60 cells. The reduced alkaloidal extract prepared from S. angulatus flowers and after acid‐base extraction showed more antitrypanosomal activity than unreduced alkaloidal extract with an IC50 value of 14.35 μg/ml and with a selectivity index of 12.23. The second most active extract was the dichloromethane extract of Crotalaria phillipsiae twigs with an IC50 value of 12.67 μg/ml and a selectivity index of 34.35. Most of the other extracts tested showed moderate antitrypanosomal activities to variable extents. Among the four pure pyrrolizidine alkaloids tested, senecionine showed moderate antitrypanosomal activity with an IC50 value of 41.78 μg/ml. Conclusions Solanecio angulatus (flowers) and Crotalaria phillipsiae (twigs) could serve as sources of novel trypanocidal compounds for the treatment of trypanosomiasis.     

Isolation of toxic and non-toxic lectins from the bitter pear melon Momordica charantia Linn

Toxic and non-toxic lectins, momordin and momordica agglutinin were isolated from Momordica charantia Linn. The mol. wt of momordin and momordica agglutinin were determined to be 23,678 and 31,762 respectively by SDS acrylamide gel electrophoresis and as gel filtration coupled with amino acid analyses. Both lectins are single polypeptide chains. The ld₅₀ of momordin was 5 mg per kg body weight and it inhibited protein biosynthesis of Ehrlich ascites tumor cells. Momordica agglutinin is able to agglutinate the human O type red blood cells at a concentration of 0·5 μg/ml. Galactose or its derivatives are able to inhibit the hemagglutination.     

INVESTIGATION OF IN VITRO TOXICITY OF JET FUELS JP-8 AND JET A

The in vitro cytotoxicity and electrophysiological toxicity of Jet Propulsion-8 (JP-8 jet fuel) on four cell types: H4IIE liver cell line, NIH Swiss 3T3 cell line, neuroblastoma × glioma NG108-15 cells, and embryonic hippocampal neurons were investigated. H4IIE cells exposed to Jet A (a commercial fuel) and JP-8 demonstrated identical toxicity with an IC₅₀ of 12.6 ± 0.4 μg/ml for the two fuels. Comparison of H4IIE and NIH/3T3 toxicity to JP-8 revealed that NIH/3T3 cells were more sensitive to JP-8 than H4IIE cells, with an IC₅₀ 8.5 ± 0.1 μg/ml. JP-8 exposure for the hippocampal neurons proved to be highly toxic (IC₅₀ of <2 μg/ml), while in contrast, the NG108-15 cells were much less sensitive. Electrophysiological examination of NG108-15 cells showed that administration of JP-8 at 1 μg/ml did not alter significantly any of the electrophysiological properties. However, exposure to JP-8 at 10 μg/ml during a current stimulus of +46 pA decreased the amplitude of the action potential to 83 ± 7% (n = 4), the rate of rise, dV/dt_MAX to 50 ± 8% (n = 4), and the spiking rate to 25 ± 11% (n = 4) of the corresponding control levels. These results demonstrate JP-8 induced cytotoxic varies among cell types. The possible mechanisms underlying these observations are presented.     

Green approach for the biosynthesis of silver nanoparticles and its antibacterial and antitumor effect against osteoblast MG-63 and breast MCF-7 cancer cell lines

The proposed study aimed to biosynthesize the silver nanoparticles (AgNPs) using aqueous leaf extract of Artocarpus integer (Family-Moraceae) The aqueous extract of A. integer was challenged with silver nitrate solution to produce silver nanoparticles. The color change of the solution confirms the formation of nanoparticles. Characterization of the nanoparticles was performed through UV–Vis spectrophotometry which showed an absorption peak at 425 nm; the FTIR analysis revealed the presence of alkenes, amines, and amides associated with the nanoparticles. Transmission electron microscopy (TEM) revealed the particle size ranges from 5.76 nm to 19.1 nm and is spherical. Thermogravimetric analysis (TGA) showed the actual protein degradation of 9.262% (ΔY) at 71.89 °C. The AgNPs were further evaluated for antibacterial activity on Staphylococcus aureus, Bacillus cereus, Salmonella entertica and Escherichia coli which exhibited good antibacterial activity when compared with ciprofloxacin. Anticancer activity was assessed by MTT assay against osteoblast MG-63 cells which showed IC50 value at 90 μg/ml against MCF-7 cells and 70 μg/ml against MG-63 cells while on normal skin fibroblast showed IC50 value at 110 μg/ml upon 24 h of incubation.