Acute kidney injury caused by the intraperitoneal injection of Bothrops jararaca venom in rats

Abstract

We examined the ability of Bothrops jararaca venom (12.5?mg/kg) injected intraperitoneally (i.p.) to cause acute kidney injury (AKI) in rats. Blood urea and creatinine (AKI biomarkers, in g dL^?1) were elevated after 2?h in venom-treated rats (urea: from 0.41?±?0.1 to 0.7?±?0.03; creatinine from 46.7?±?3.1 to 85?±?6.7; p?<?0.05; n?=?3 each), with no change in circulating reduced glutathione. Venom-treated rats survived for ～6?h, at which point platelets were reduced (×10³ µL^?1; from 763.8?±?30.2 to 52.5?±?18.2) whereas leukocytes and erythrocytes were slightly increased (from 4.7?±?0.3 to 6.6?±?0.1?×?10³?µL^?1 and from 8.38?±?0.1 to 9.2?±?0.09?×?10⁶?µL^?1, respectively; p?<?0.05); blood protein (5.2?±?0.4?g dL^?1) and albumin (2.7?±?0.1?g dL^?1) were normal, whereas blood and urinary urea and creatinine were increased. All parameters returned to normal with antivenom given 2?h post-envenomation. The i.p. injection of venom caused AKI similar to that seen with other routes of administration.     

Bioequivalence evaluation of Florfenicol pharmaceutics in pigs using liquid chromatography-tandem mass spectrometry

The bioequivalence of two Florfenicol (FF) products in pigs was evaluated. A 2?×?2 crossover trial with a 14 days wash-out period was performed. The pigs were orally administered in a single dose (2?mg/kg b.w of FF). Serum samples were analyzed using a liquid chromatography-tandem mass spectrometry method. The limit of quantification was 0.1?ng/mL, and the calibration range was 1.0–100.0?ng/mL. Furthermore, intraday and interday were 5.43–9.09% and 6.23–9.68%, respectively. The areas under the curve (AUC_0–48) for the test product B of FF and reference product A were 7289.61?±?1750.44 and 6545.01?±?2766.25?h?×?ng/mL, respectively. The highest concentrations of FF in the serum (C_max) were 726.05?±?211.77 and 641.97?±?117.94?ng/mL. The mean retention times (MRT) was 7.91?±?1.98 and 7.76?±?2.89?h while the half-lives (T_1/2) were 4.07?±?1.71 and 4.99?±?3.30?h. From the analysis of variance results, the p values of C_max and AUC_0–∞ for the 90% confidence interval were 0.492 and 0.320 (p?>?0.05), respectively. A comparison between the test product and the reference product showed no significant difference. Both products showed bioequivalence after being administered in pigs.     

Anti-glycating and anti-oxidant compounds from traditionally used anti-diabetic plant Geigeria alata(DC) Oliv. & Hiern.

Abstract

A new sesquiterpene lactone geigerianoloide (1) and four known flavonoids axillarin (2), quercetin (3), 3-methoxy-5,7,3',4'-tetrahydroxy-flavone (4) and hispidulin (5) were isolated from Geigeria alata (DC) Oliv. & Hiern. (Asteraceae). Structures were deduced using ¹H- and ¹³C- NMR spectroscopy, mass spectrometry, while the structure of compound 1 was also deduced using X-ray crystallography technique.

Geigeria alata is traditionally used for diabetes, therefore compounds were tested for anti-glycation activity, in which compounds 2 and 3 showed potent activities (IC₅₀ values of 246.97?±?0.83 and 262.37?±?0.22 µM, respectively) compared to IC₅₀ value 294.50?±?1.5 µM of rutin. Moreover, compound 4 exhibited a comparable activity to rutin (IC₅₀?=?293.28?±?1.34 µM). Compound 5 showed a weak activity.

Compounds 2, 3, and 4 exhibited potent DPPH radical scavenging activity (IC₅₀?=?0.1?±?0.00, 0.13?±?0.00 and 0.15?±?0.01 µM, respectively). Compounds 2, 3, and 4 demonstrated significant superoxide anion scavenging activity with IC₅₀ values of 0.14?±?0.001, 0.17?±?0.00, and 0.11?±?0.006 µM, respectively.     

Synthesis,characterization, and hypoglycemic efficacy of nitro and amino acridines and 4-phenylquinoline on starch hydrolyzing compounds: an in silico and in vitro study

α-Amylase and α-Glucosidase are important therapeutic targets for type II diabetes. The present focus of our study is to elucidate the hypoglycemic activity of novel compounds through in vitro and in silico studies. Here, we synthesized the nitro acridines (3a–3c), amino acridines (4a–4c), and nitro phenylquinoline (3d) and amino phenylquinoline (4d) using a multi-step reaction protocol in good yields. All the above derivatives were screened for molecular docking, α-Amylase and α-Glucosidase inhibitory activities utilizing acarbose as standard drug. In silico studies were performed to explore the binding ability of compounds with the active site of α-Amylase and α-Glucosidase enzymes. The in vitro antihyperglycemic report of 3c exhibits the maximum inhibitory activity with IC₅₀ values of 200.61?±?9.71 μmol/mL and 197.76?±?8.22 μmol/mL against α-Amylase and α-Glucosidase, respectively. Similarly, the compound 3a exhibits IC₅₀ values of 243.78?±?13.25 μmol/mL and 296.57?±?10.66 μmol/mL, and 4c exhibits IC₅₀ values of 304.28?±?3.51 μmol/mL and 278.86?±?3.24 μmol/mL with a significant p?<?0.05 in both enzyme inhibitions. In addition, the presence of diverse functional moieties in synthesized compounds may provide a strong inhibitory action against the abovementioned enzymes compared with standard acarbose inhibition (IC₅₀, 58.74?±?3.68 μmol/mL and 49.39?±?4.94 μmol/mL). Also, the docking studies provided an excellent support for our in vitro studies. The outcome of these studies recommends that the tested compounds might be treated as potential inhibitors for the starch hydrolyzing enzymes in type II diabetes.

     

Toxic mineral elements in Mytilus galloprovincialis from Sicilian coasts (Southern Italy)

Abstract

We assessed the relationship between V, Cr, Mn, Hg, As, Cd, Sn, Sb and Pb concentrations in Mytilus galloprovincialis samples from the coasts of Sicily and the expression of metallothioneins. Toxic mineral elements assessment was carried out by A.A. Spectrometry and ICP-MS. The metallothioneins expression was performed by q-PCR method. Low metals’ levels were found in the mussel samples examined, in comparison with what was reported in literature. The highest mean values of toxic mineral elements were found in Gela (Cr 0.178?±?0.03?mg/Kg, Mn 4.325?±?0.012?mg/Kg, As 3.706?±?0.009?mg/Kg, Sn 0.148?±?0.014?mg/Kg, Sb 0.009?±?0.004?mg/Kg e Pb 0.364?±?0.01?mg/Kg). Significant levels of Hg were found in samples from Catania (0.014?±?0.005?mg/Kg). Only vanadium and lead concentrations showed significant differences between sampling areas (p?<?0.05). Molecular analysis verified a basal expression of Mt1 and the absence of over-expression of Mt2, confirming the low mineral’s concentrations found in the samples examined.     

Two new aromatic polyketides from a deep-sea fungus Penicillium sp. SCSIO 06720

Abstract

Two new compounds, 5-[2-hydroxypropane-1-yl]-2,6-dimethlbenzene-1,3-diol (1) and coniochaetone L (2), together with 19 known compounds (3–21), were isolated from a deep-sea fungus, Penicillium sp. SCSIO 06720. Their structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analyses, chiral-phase HPLC analysis, and electronic circular dichroism spectra. All the isolated compounds (1–21) were tested for their antibacterial and HIV latency-reversal activities. Among these compounds, compound 16 showed moderate antibacterial activities against Staphylococcus aureus ATCC 29213 and Methicillin-Resistant Staphylococcus Aureus-shh-1 with MIC values of 10.4?±?3.7?μg/mL and 46.9?±?29.7?μg/mL, respectively, which were comparable to that of the positive control ampicillin with MIC values of 0.5?±?0.4?μg/mL and 2.7?±?0.9?μg/mL, respectively.     

Elemental Analysis and Metal Intake of Romanian Vegetables

ABSTRACT

Inductively coupled plasma-mass spectrometry multielemental profiling was performed to determine eight elements in 54 vegetable samples. The range of concentrations of Fe and Ni was 1.91?±?0.09 to 443.31?±?22.32?mg/kg and 0.05?±?0.004 to 16.36?±?0.36?mg/kg, respectively. The concentrations of Pb and Cd were up to 1.56?±?0.04 and 0.78?±?0.04?mg/kg, respectively. Some samples exceeded the maximum admissible limits imposed by national and international regulations. The mean concentrations of Mn and Cu were between 20.93?±?0.43 and 13.98?±?0.30?mg/kg in tomatoes and 20.60?±?0.53 and 11.25?±?0.22?mg/kg in peppers. For the evaluation of health risk related to the consumption of vegetables, the daily intake rate, target hazard quotient (THQ), and hazard index were evaluated. The daily intakes were low and correspond to 2 to 14% of the tolerable daily values established by legislation. The results showed that the THQ and hazard index for the metals were lower than 1, indicating that the vegetable ingestion does not represent a significant risk for consumer health. Analysis of variance revealed that Zn may be used as a species-specific marker (p?=?0.026). Principal component analysis extracted three main components, explaining a total variance of 72.49% and grouped all determined elements.     

Synthesis,EGFR-TK inhibition and anticancer activity of new quinoxaline derivatives

Abstract

Ethyl 4-substituted-3-oxo-quinoxaline-2-carboxylates 3–5 were obtained via alkylation of ethyl 3-oxo-3,4-dihydroquinoxaline-2-carboxylate (1). Compound 1 was heterocyclized using hydrazines, ethylenediamine, and ethanolamine to give pyrazoloquinoxalines 6, 7, diazepinoquinoxaline 8, and oxazepinoquinoxaline 10. The quinoxaline-2-carboxamides 9, 11, 12 were prepared via condensation of compound 1 with different amines. Compound 1 was thiated using Lawesson’s reagent affording quinoxaline-3-thione 13, in fair yield. In addition, the reaction of 4-methyl-3-oxoquinoxaline 3 with some binucleophiles led to a series of new oxoquinoxaline derivatives 14–18. The molecular structure of compounds 1, 3, and 9 was confirmed by X-ray crystallography.

The anti-proliferative activity showed that among all the tested compounds, compounds 3, (IC₅₀ 2.51?±?3.0, 4.22?±?1.6 and 2.27?±?1.9?µM), 11 (IC₅₀ 1.32?±?2.61, 1.41?±?1.23 and 1.18?±?1.91?µM) and 17 (IC₅₀ 1.72?±?1.32, 1.85?±?0.94 and 1.92?±?4.83?µM) showed noteworthy anti-proliferative effects against the three cancer cell lines, HCT116, HePG2 and MCF7, respectively, compared to the reference drugs doxorubicin (IC₅₀ 1.41?±?0.58, 0.90?±?0.62 and 1.01?±?3.02?µM) and erlotinib (IC₅₀ 1.63?±?0.81, 1.57?±?0.62 and 1.49?±?0.54?µM). Compounds 3 (0.899?nM), 11 (0.508?nM) and 17 (0.807) showed strong EGFR inhibitory activity compared to Erlotinib (0.439?nM) and these results are in agreement with the docking study. These results suggest that compounds could probably be promising anticancer agents with EGFR inhibitory activity.     

Optimization of ultrasound-assisted extraction of phenolic compounds from Sesamum indicum

Abstract

Effective extraction of phyto-biomolecules insures retaining maximum functionality along with higher recovery. In this study, ultrasound-solvent assisted extraction (USAE) was employed for optimal extraction of phyto-biomolecules from Sesamum indicum (sesame) leaves using the approach of Response Surface Methodology (RSM). The optimized condition of 200?W power, 59% methanol concentration with 1:14?g/mL solid–liquid ratio and 15?min of extraction time yielded 367.39?±?1.85?mg GAE/100?g of total phenolic content, 96.72?±?3.27% of free radical scavenging activity and 81.20?±?2.87% of iron chelating activity respectively. The extract consist of essential phytocomponents like gallic acid, chlorogenic acid, and quercetin with lipid peroxidation activities of >50% over incubation time of 48?h. Also, showed antimicrobial activity against various Gram’s negative and positive food borne pathogens. The results of this study implied the importance of USAE for effective and optimum recovery of phyto-biomolecules from Sesame leaves with retained functional properties.     

An insight into chemical composition and bioactivity of 'Prokupac' red wine

Abstract

Autochthonous variety 'Prokupac' (Vitis vinifera L.) red wines with the addition of selected aromatic herbs (Artemisia absinthium, Cinnamomum zeylanicum, Glycyrrhiza glabra and Pimpinella anisum L.) were evaluated for chemical composition and biological activity. Furthermore, their polyphenolic profiles were determined by HPLC-DAD. While total phenolic (TPC) and flavonoid (TFC) contents, along with antioxidant activity, were significantly higher in all examined wine samples, the content of total anthocyanins was decreased, compared to a pure 'Prokupac' wine, used as the control one. On the other hand, 'Prokupac' wines with the addition of cinnamon (S. zeylanicum) and wormwood (A. absinthium) displayed highest antioxidant (EC₅₀, 0.021?±?0.001?mg/mL) and antibacterial (Enterococcus faecalis, MIC/MBC 15.63/62.50?μL/mL) activities, respectively. The study showed that 'Prokupac' wine with the addition of cinnamon was significantly enriched both with TPC and TFC, compared to control wine (p?<?0.05), which may contribute to its market potential.     

Determination of acetylcholinesterase and α-glucosidase inhibition by electrophoretically-mediated microanalysis and phenolic profile by HPLC-ESI-MS/MS of fruit juices from Brazilian Myrtaceae Plinia cauliflora (Mart.) Kausel and Eugenia uniflora L.

Abstract

Alzheimer’s disease and diabetes mellitus are contemporary diseases of great concern. Phenolic compounds are linked to several health benefits and could lead to novel strategies to combat these ailments. The objective of this study was to evaluate by electrophoretically-mediated microanalysis the potential inhibitory activity of the fruit juices from Plinia cauliflora (“jaboticaba”) and Eugenia uniflora (“pitanga”) toward acetylcholinesterase (AChE) and α-glucosidase, target enzymes in strategies for the treatment of these diseases. The phenolic profiles of the samples were also investigated. Jaboticaba and pitanga juices inhibited 85.90?±?1.73 and 52.67?±?1.24% of AChE activity at 5?mg mL^?1, and 57.91?±?2.60 and 69.47?±?2.89% of α-glucosidase activity at 1?mg mL^?1, respectively. Total phenolic content of the juices were 303.54?±?28.28 and 367.00?±?11.42 mgGA L^?1, respectively. The observed inhibitory activity can be explained, at least in part, by the presence of the phenolic compounds.     

Chemical composition and antifungal activity of essential oils from Senecio nutans,Senecio viridis,Tagetes terniflora and Aloysia gratissima against toxigenic Aspergillus and Fusarium species

Abstract

Essential oils from aerial parts of Senecio nutans, Senecio viridis, Tagetes terniflora and Aloysia gratissima were analysed by GC-MS and their antifungal activities were assayed on toxigenic Fusarium and Aspergillus species. Sabinene (27.6?±?0.1%), α-phellandrene (15.7?±?0.3%), o-cymene (9.6?±?0.2%) and β-pinene (6.1?±?0.2%) in S. nutans, 9,10-dehydrofukinone (92.7?±?0.2%) in S. viridis, β-thujone (36.1?±?0.1%), α-thujone (32.2?±?0.2%), 1,8-cineol (10.7?±?0.1%) and sabinene (6.2?±?0.2%) in A. gratissima, and cis-tagetone (33.6?±?0.2%), cis-β-ocimene (17.1?±?0.2%), trans-tagetone (17.0?±?0.1%), cis-ocimenone (8.0?±?0.2%) and trans-ocimenone (8.2?±?0.1%) in T. terniflora. The oils showed moderate antifungal activity (1.2?mg/mL?>?MIC >0.6?mg/mL) on the Fusarium species and a weak effect on Aspergillus species. The antifungal activity was associated on F. verticillioides to the high content of cis-tagetone, trans-tagetone, cis-β-ocimene, cis-ocimenone, trans-ocimenone and on F. graminearum due to the total content of oxygenated sesquiterpenes and 9,10- dehydrofukinone. The oil of S. viridis synergized the effect of fungicides and food preservatives on F. verticillioides.

     

Protolytic properties and complexation with copper(II) ions of some azo derivatives of β-arylaminopropionic acids

The azo coupling reaction of N-(2-carboxyethyl)anthranilic acid and N,N,N′,N′-tetrabis(2-carboxyethyl)-1,3-phenylenediamine with diazosulfanilic acid yielded the complexones sodium 4-N-(2-carboxyethyl)amino-5-carboxyazobenzene-4′-sulfonate (I) and 2,4-N,N,N′,N′-tetrabis(2-carboxyethyl)diaminoazobenzene-4′-sulfonic acid (II), respectively. The acidity constants of I and II (20°C, μ = 0.1M KCl) were determined to be as follows: for I, pK ₀₀ = 1.29 ± 0.13, pK ₀ = 2.92 ± 0.07, pK ₁ = 3.92 ± 0.05, pK ₂ = 5.16 ± 0.03; for II, pK ₀₀ = 2.35 ± 0.06, pK ₀ = 2.81 ± 0.09, pK ₁ = 3.21 ± 0.11, pK ₂ = 3.81 ± 0.09, pK ₃ = 4.34 ± 0.04, pK ₄ = 5.03 ± 0.06, pK ₅ = 6.67 ± 0.07. The electronic absorption spectra of I and II were measured, and acid-base equilibrium scheme for I and II in aqueous solutions were suggested. The complexation constants of I and II with copper(II) ions were determined to be logK _CuQ^I= 5.47 ± 0.06 and logK _CuQ^II= 5.72 ± 0.13 (20°C, μ = 0.1 M KCl).     

Rasagiline-encapsulated chitosan-coated PLGA nanoparticles targeted to the brain in the treatment of parkinson's disease

The aim of this study was to investigate the brain targeting potential of rasagiline-encapsulated chitosan-coated PLGA nanoparticles (RSG-CS-PLGA-NPs) delivered intranasally into the brain. Chitosan-coated PLGA nanoparticles (RSG-CS-PLGA-NPs) were developed through double emulsification-solvent evaporation technique. RSG-CS-PLGA-NPs were characterized for particle size, zeta potential, size distribution, encapsulation efficiency, and in vitro drug release. The mean particle size, polydispersity index, and encapsulation efficiency were found to be 122.38?±?3.64, 0.212?±?0.009, and 75.83?±?3.76, respectively. High-performance liquid chromatography–mass spectroscopy and mass spectroscopy study showed a significantly high mucoadhesive potential of RSG-CS-PLGA-NPs and least for conventional and homogenized nanoformulation. Pharmacokinetic results of RSG-CS-PLGA-NPs in Wistar rat brain and plasma showed a significantly high (**p?<?0.005) AUC_0-24 and amplified C_max over intravenous treatment group. Finally, the investigation demonstrated that intranasal delivery of mucoadhesive nanocarrier showed significant enhancement of bioavailability in brain, after administration of the RSG-CS-PLGA-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson’s disease therapy and related brain disorders.     

Three new phenylacetamide glycosides from Dracocephalum tanguticum Maxim and their anti-hyperglycemic activity

Abstract

Three new phenylacetamide glycosides (1–3) together with one known phenylacetamide glycoside (4) and two known flavonoid glycosides (5–6) were isolated from whole plants of Dracocephalum tanguticum. The structure of all compounds were elucidated based on spectroscopic data analysis and comparison with data reported in related literature. Compounds (1–3) were evaluated for their anti-hyperglycemic and anti-fungal (Candida albicans) activities, the results revealed that all of them showed moderate activity with 3T3-L1 adipocytes glucose consumption rate of 20.80?±?1.47%, 21.48?±?2.44%, and 21.57?±?1.35%, respectively at the final concentration of 25?μM. However, none of them showed obvious Candida albicans inhibitory activity.     

Kinetic and mechanistic studies of the reactivity of iron(IV) TAMLs toward organic sulfides in water: resolving a fast catalysis versus slower single-turnover reactivity dilemma

TAML complex is oxidized by H₂O₂ or ^tBuOOH in water at pH < 10 into the corresponding iron(IV) μ-oxo-bridged dimer 2, which oxidizes readily ring-substituted thioanisoles p-XC₆H₄SMe (X=H, MeO, Me, Cl, CN) into the corresponding sulfoxides with regeneration of 1. The oxidation studied under pseudo-first-order conditions using the stopped-flow technique by monitoring the fading of the 420-nm band of 2 follows hyperbolic kinetics according to the rate law k_obs = ab[p-XC₆H₄SMe]/(1 + b[p-XC₆H₄SMe]) at pH 8 and 25 °C. Parameters a, b, and ab all decrease for electron-poorer thioanisoles and the Hammett value ρ?~?1 has been found for ab, which can be associated with the second-order rate constants for oxidation of thioanisoles by 2. The kinetics of oxidation of p-NO₂C₆H₄SMe by H₂O₂ catalyzed by 1 has been studied under steady-state conditions. Covering the concentration of 1 in a 100-fold range has revealed that though first-order kinetics in 1 is observed at low catalyst concentrations (below 10^?6 M), there is a significant negative deviation from linearity at [1]?>?10^?6 M. The latter was rationalized by the equilibrium between the monomeric and dimeric Fe^IV species 2 M???M–M (K_d), both being able to oxidize p-NO₂C₆H₄SMe with rate constants k_m and k_d which were found to be (13?±?1)?×?10⁴ and (0.32 ± 0.01)?×?10⁴ M^?1 s^?1, respectively. The difference in the rate constants is the key for resolving the dilemma of faster catalysis versus slower single-turnover reactivity of TAML activators in water.     

1,2-Benzisoxazole-3-acetamide derivatives as dual agents for DPP-IV inhibition and anticancer activity

Abstract

Herein, we have designed various benzisoxazole acetamide derivatives with and without glycine spacer as DPP-IV inhibitors. Compounds 9a–d and 11a–e were synthesized and screened for their in vitro DPP-IV inhibition. Compounds 11a and 11c showed moderate activity for DPP-IV inhibition, whereas other remained inactive at 25–200?µM concentrations. DPP-IV inhibition can be a good strategy for modulating diabetes and cancer; hence, we have screened compounds 9a–d and 11a–e for their anticancer activity using MTT assay against A549 and MCF7 cell lines. Compounds 9a–d without glycine spacer have shown good anticancer activity compared to compounds 11a–e with glycine spacer. Compound 9b has shown moderate activity with IC₅₀ values 4.72?±?0.72 and 4.39?±?0.809?µM against A549 and MCF7 cell lines, respectively. Interestingly, compound 9c with cyano group has shown very good anticancer activity with IC₅₀ 2.36?±?0.34?µM against MCF7 cell line as compared to fluorouracil with IC₅₀ 45.04?±?1.02?µM.     

Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit

Novel 4,5-dihydropyrazole derivatives (3a–i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a–i). The addition–cyclization of 2,4′-dibromoacetophenone (4) to pyrazole derivatives (3a–i) gave the new pyrazolyl-thiazole derivatives (5a–i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a–i and 5a–i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with K_i values in the range of 18.90?±?2.37 ?58.25?±?13.62?nM for hCA II and 5.72?±?0.98 ?37.67?±?5.54?nM for hCA I. Also, the K_i parameters of these compounds for AChE were obtained in the range of 25.47?±?11.11???255.74?±?82.20?nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed K_i value of 70.55?±?12.30?nM against hCA II, and 67.17?±?9.1?nM against hCA I, and tacrine inhibited AChE showed K_i value of 263.67?±?91.95.     

Cytotoxicity,apoptosis, interaction with DNA,cellular uptake,and cell cycle arrest of ruthenium(II) polypyridyl complexes containing 4,4′-dimethyl-2,2′-bipyridine as ancillary ligand

Two new ruthenium(II) polypyridyl complexes, [Ru(dmb)₂(DNPIP)](ClO₄)₂ (1) (DNPIP?=?2-(2,4-dinitrophenyl)imidazo[4,5-f][1,10]phenanthroline, dmb?=?4,4′-dimethyl-2,2′-bipyridine) and [Ru(dmb)₂(DAPIP)](ClO₄)₂ (2) (DAPIP?=?2-(2,4-diaminophenyl)imidazo[4,5f][1,10]phenanthroline), were synthesized and characterized. The DNA-binding behaviors of these complexes have been studied by UV-Vis absorption titration, viscosity measurements, and photocleavage. The DNA-binding constants are 7.39 (±0.16)?×?10⁴ (s?=?2.68) and 2.73 (±0.16)?×?10^4?(mol?L^?1)^?1 (s?=?0.64) for 1 and 2, respectively. Their evaluation as cytotoxic agents on different cancer cell lines was investigated with IC₅₀ values of 59.5, 51.3, and 70.3?µmol?L^?1 for 1, >100, 87.9, and 77.9?µmol?L^?1 for 2 against BEL-7402, HepG-2, and MCF-7 cells, respectively. Complex 1 is more active than 2 against selected cancer cell lines. The apoptosis induced by these complexes was studied. Cellular uptake showed that these complexes could enter into the cytoplasm and accumulate in the nuclei. The cell cycle arrest and antioxidant activity against hydroxyl radicals were also investigated.     

Antifungal activity of compounds isolated from Aspergillus niger and their molecular docking studies with tomatinase

Abstract

Using a dual culture antagonism assay, Aspergillus niger exhibited 51.5?±?1.1% growth inhibition against Fusarium oxysporum f.sp. lycopersici, the wilt pathogen of tomato. For enhanced production of antifungal metabolites, nutrient optimization was performed and in vitro well-diffusion antifungal assays demonstrated that crude extract obtained from GPYB culture showed a maximum zone of inhibition (8.8?±?0.4?mm) against the wilt pathogen, which is corroborated by the comparative LCMS profiles of the extracts from all three media i.e. GPYB, YEB and PDB. Two known compounds, Asperazine (m/z 665 [M?+?H]⁺) and Nigerone (m/z 571 [M?+?H]⁺), were isolated from A. niger and their antifungal activity is reported here for the first time. In MIC experiments, Asperazine and Nigerone inhibited the pathogen at 60 and 80?µg·mL^?1 respectively. Molecular docking studies of Nigerone and Asperazine with F. oxysporum tomatinase showed five and six binding interactions respectively.