CORD-19_Custom_license_subset  

CORD-19:0a04d377a83b28dbc0d97c90acd829255796f69c JSONTXT 9 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function

Id Subject Object Predicate Lexical cue
T1 0-141 Sentence denotes Journal Pre-proof Anticancer activity studies of novel metal complexes of ligands derived from polycyclic aromatic compound via greener route
T2 143-151 Sentence denotes Abstract
T3 154-298 Sentence denotes Remedy for cancer is certainly one of the big medical challenges to the scientists of 21 st century and is one of the current research hotspots.
T4 299-420 Sentence denotes The escalating research to fight against cancer is getting us closer to a future, where cancer becomes a curable disease.
T5 421-614 Sentence denotes As a researcher, we dream of curing cancer as easy as the deadly diseases viz., chickenpox, smallpox, polio, measles, sars (severe acute respiratory syndrome), yellow fever, malaria etc., [1] .
T6 615-751 Sentence denotes Although existing drugs show efficacy, their lack of selectivity for tumor cells over normal cells can lead to severe side effects [2] .
T7 752-828 Sentence denotes Cancer is caused by mutations that transform healthy cells into tumor cells.
T8 829-924 Sentence denotes Recent studies have demonstrated that there will not be a match between tumors of two patients.
T9 925-1026 Sentence denotes It implies that the scientists should work on medicines that are tailored to cure a specific patient.
T10 1027-1215 Sentence denotes Platinum based drugs are actively used in treating various types of cancers; however, drug resistance, adverse side effects and low specificity are common in platinum chemotherapy [3, 4] .
T11 1216-1371 Sentence denotes To overcome these abnormalities to great extent, in recent years other metal based drugs have been developed and tested for their anticancer efficacy [5] .
T12 1372-1534 Sentence denotes Important ones are the coordination compounds of Ni(II), Cu(II), Zn(II) and Ru(II) which can overcome the limited activity of cisplatin and its analogous [6, 7] .
T13 1535-1654 Sentence denotes Our current research puts in effort to crack a new anticancer drug candidate which could prove to be a better medicine.
T14 1655-1857 Sentence denotes In our present work, the hydrazone Schiff base ligands derived from 9-oxo-9H-fluorene-1-carboxylic acid and their respective Co(II), Cu(II) and Ni (II) complexes are synthesized impeccably and analyzed.
T15 1858-1925 Sentence denotes Hydrazones play an important role in inorganic medicinal chemistry.
T16 1926-2064 Sentence denotes They can easily form stable complexes with transition metal ions and can exhibit interesting photophysical and biological properties [8] .
T17 2065-2230 Sentence denotes They exhibit biological activities such as antibacterial [9] , antioxidant [10] , antifungal [11] , antitubercular [12] , antiinflammatory [13] and anticancer [14] .
T18 2231-2333 Sentence denotes Fluorenone is no doubt a polycyclic aromatic compound, one could doubt about its therapeutic property.
T19 2334-2441 Sentence denotes But the literature reveals that derivatives of fluorenone have exhibited interesting biological activities.
T20 2442-2565 Sentence denotes Arylsulfonylspiro[fluorene-9,5΄-imidazolidine]-2΄,4΄-diones are found to be effective as aldose reductase inhibitors [15] .
T21 2566-2709 Sentence denotes Azabenzo[a]fluorene-5,6-diones have comparable cytotoxicities against cancer cell lines in vitro, with that of standard drug doxorubicin [16] .
T22 2710-2982 Sentence denotes Our previous publication [17] have successfully established the anticancer efficacy of copper complex of fluorenone based ligand; which exhibited better anticancer activity against human breast carcinoma (MCF-7) cell line when compared to that of standard drug paclitaxel.
T23 2983-3128 Sentence denotes These results prompted us to synthesize new ligands which are embedded with fluorenone moiety, carboxylic acid, carboxamide and hydrazone groups.
T24 3129-3233 Sentence denotes The metal complexes are synthesized from these ligands via eco-friendly routes employing green solvents.
T25 3234-3435 Sentence denotes The ligands and respective metal complexes were tested for their anticancer activities with MTT assay against breast cancer (MCF-7) cell line, DNA cleavage study was performed using pBR322 plasmid DNA.
T26 3436-3530 Sentence denotes Antioxidant activity study was carried out through DPPH free radical-scavenging ability assay.
T27 3531-3632 Sentence denotes Molecular docking studies were also carried out to examine the bonding mode of synthesized compounds.
T28 3633-3780 Sentence denotes All the raw materials including reagents, catalysts, solvents and drying agents were of fine chemical grade and utilized as received by the vendor.
T29 3781-3908 Sentence denotes The MTT [2-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl-2H-tetrazol-3-ium bromide] dye was purchased from Sigma, St. Louis, MO, USA.
T30 3909-4054 Sentence denotes Infrared (IR) spectra of the synthesized materials were recorded in the range of 4000-550 cm -1 with PerkinElmer Spectrum Two FT-IR spectrometer.
T31 4055-4227 Sentence denotes By using TMS as internal reference compound, 1 H and 13 C NMR spectra were recorded in DMSO-d 6 solvent on JEOL 400 MHz and Bruker 400 MHz spectrometer at room temperature.
T32 4228-4318 Sentence denotes Using ThermoQuest Elemental Analyzer, elemental analyses of the compounds was carried out.
T33 4319-4470 Sentence denotes Electronic spectra of ligands and their metal complexes were recorded on a PerkinElmer LAMBDA 365 UV-Vis spectrophotometer in the range of 1100-200 nm.
T34 4471-4632 Sentence denotes Thermal analysis of the metal complexes was carried out with an SDT Q600 analyzer, by increasing the temperature from RT to 1000 °C at the rate of 10 °C min -1 .
T35 4633-4795 Sentence denotes The molar conductance measurements were made on ELICO CM 180 conductivity meter with a cell constant of 1.0 after calibration with standard KCl solution at 25 °C.
T36 4796-4863 Sentence denotes LC-ESI-MS spectra were recorded on LCMS 2010A, SHIMADZU instrument.
T37 4864-5040 Sentence denotes 9-Oxo-9H-fluorene-1-carboxylic acid is prepared from fluoranthene using potassium dichromate as an oxidizing agent as per the protocol reported in our previous publication [18]
T38 5042-5260 Sentence denotes An equimolar mixture of 9-oxo-9H-fluorene-1-carboxylic acid (2.5 g, 11.15 mmol) and benzohydrazides (4-methoxy and 4-tert-butyl derivatives) (11.15 mmol) is refluxed in 50 mL methanol at 70 °C for 8 h (Scheme 1) [19] .
T39 5261-5302 Sentence denotes The contents are partially soluble at RT.
T40 5303-5458 Sentence denotes About 30 min of heating at 70 °C, the reaction mixture turns orange to yellow and yellow solids separate, which indicates the formation of desired product.
T41 5459-5497 Sentence denotes The reaction is monitored by TLC in 9:
T42 5498-5521 Sentence denotes 1 chloroform: methanol.
T43 5522-5607 Sentence denotes The solids are filtered and washed with cold methanol and dried under vacuo at 40 °C.
T44 5608-5614 Sentence denotes L 1 H:
T45 5615-5621 Sentence denotes Yield:
T46 5622-5633 Sentence denotes 3.9 g; 94%.
T47 5634-5640 Sentence denotes Color:
T48 5641-5655 Sentence denotes Canary yellow.
T49 5656-5662 Sentence denotes L 2 H:
T50 5663-5669 Sentence denotes Yield:
T51 5670-5681 Sentence denotes 4.1 g; 92%.
T52 5682-5688 Sentence denotes Color:
T53 5689-5703 Sentence denotes Canary yellow.
T54 5704-5724 Sentence denotes Copper (II) complex:
T55 5725-5795 Sentence denotes The copper(II) complexes are synthesized in water at room temperature.
T56 5797-6017 Sentence denotes The effect of ligands and their metal complexes on the viability of breast cancer cells was determined using the standard colorimetric MTT [2-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl-2Htetrazol-3-ium bromide] assay [20] .
T57 6018-6275 Sentence denotes The monolayer cell culture was trypsinized and the cell count was adjusted to 1.0 X 10 5 cellsmL -1 using DMEM (Dulbecco's Modified Eagle Medium) containing 10% FBS and seeded to 96-well microtiter plates (Falcon, Becton-Dickinson, Franklin Lakes, NJ, USA).
T58 6276-6334 Sentence denotes After 24 h; of plating, cells were serum starved for 24 h.
T59 6335-6503 Sentence denotes Respective concentrations (10, 20, 30, 40 and 50 µgmL -1 ) of ligands and their metal complexes were added to serum free medium and the assay was terminated after 48 h.
T60 6504-6692 Sentence denotes Medium was removed and 200 µL of DMSO was added and the amount of formazan formed was measured at 595 nm on a 6 Model 680 microplate reader (Bio-Rad Laboratories, Inc., Hercules, CA, USA).
T61 6693-6908 Sentence denotes The percentage growth inhibition was calculated using the following formula and concentration of test drug needed to inhibit cell growth by 50% (IC 50 ) is generated from the dose-response curves for each cell line.
T62 6909-7039 Sentence denotes This assay is based on the reduction of MTT by the mitochondrial dehydrogenase of intact cells to a purple formazan product [21] .
T63 7040-7103 Sentence denotes Inhibition Percentage = OD of Test sample ÷ OD of control × 100
T64 7104-7229 Sentence denotes All experiments were performed in triplicates (n = 3) and the numerical data are presented as mean ± standard deviation (SD).
T65 7230-7509 Sentence denotes The DNA cleavage activity of the newly synthesized ligands and their metal complexes was monitored by Agarose gel electrophoresis on pBR322 DNA (200 ng) in TAE buffer (40 mM Tris-Acetate, 1 mM EDTA) to yield a total volume of 10 µL and then incubated in dark for 30 min at 37 °C.
T66 7510-7589 Sentence denotes Different concentrations of compounds were tested; 10, 30, 50 and 100 µgmL -1 .
T67 7590-7764 Sentence denotes The reaction was incubated at 37 °C for 2 h and 3 µL of loading buffer (bromophenol blue in H 2 O) was added to each tube and the mixed samples were loaded on 1% Agarose gel.
T68 7765-7854 Sentence denotes The electrophoresis was carried out for 2 h at 50 V in Tris-acetate-EDTA buffer (pH 8.3).
T69 7855-7989 Sentence denotes After electrophoresis, the gel was stained with Ethidium bromide (EB) for 30 min prior to being photographed under UV light [22, 23] .
T70 7990-8132 Sentence denotes The cleavage properties were determined based on the ability of compounds to convert the supercoiled form (Form I) into nicked form (Form II).
T71 8133-8200 Sentence denotes The results were compared with standard DNA marker and control DNA.
T72 8201-8294 Sentence denotes In the present anticancer docking study B-cell lymphoma-extra large (BCl-XL) protein (PDB ID:
T73 8295-8458 Sentence denotes 3ZK6) was used as drug target in molecular docking studies to computationally prove the anticancer potentialities of newly synthesized metal complexes and ligands.
T74 8459-8589 Sentence denotes The crystal structure of the BCL-XL protein bound to its respective inhibitor was collected from Protein Data Bank (PDB) database.
T75 8590-8676 Sentence denotes The site to which the inhibitor molecule was bound was identified using PDBSum server.
T76 8677-8788 Sentence denotes Optimization of target protein by removal ligands and hetero atoms was carried out using Discovery Studio tool.
T77 8789-8898 Sentence denotes 3D coordinates files of newly synthesized compounds in ".pdb" format were generated using marvin sketch tool.
T78 8899-8992 Sentence denotes Further these files were converted from ".pdb" to ".pdbqt" file format using Autodock 4 tool.
T79 8993-9212 Sentence denotes Automated molecular docking was carried out to determine the best orientation of the newly synthesized compounds possessing anti-cancer property was hypothesized as inhibitors bound in the active site of BCL-XL protein.
T80 9213-9304 Sentence denotes A Lamarckian genetic algorithm implemented in the Auto Dock 4.0 program was employed [24] .
T81 9306-9492 Sentence denotes In the present study, radical scavenging activity of ligands and their respective metal complexes was evaluated using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical as a reagent [26] .
T82 9493-9614 Sentence denotes Required volume of a DPPH radical solution in ethanol (60 µM) was mixed with different concentrations of testing samples.
T83 9615-9680 Sentence denotes The mixture was incubated for 30 min in dark at room temperature.
T84 9681-9798 Sentence denotes After the incubation, the absorbance of the reaction mixture was measured at 517 nm using a UV-Vis Spectrophotometer.
T85 9799-9871 Sentence denotes For the positive control ascorbic acid was used as a reference standard.
T86 9872-9960 Sentence denotes The DPPH scavenging activity of each sample was calculated using the following equation:
T87 9961-10112 Sentence denotes Where, A c is the absorbance of the control reaction (100 µL of ethanol with 100 µL of the DPPH solution) and A t is the absorbance of the test sample.
T88 10113-10151 Sentence denotes The experiment was done in triplicate.
T89 10152-10203 Sentence denotes The IC 50 value was calculated for all the samples.
T90 10204-10284 Sentence denotes Lower absorbance of the reaction mixture indicates higher free radical activity.
T91 10285-10465 Sentence denotes To identify the bonding mode as well as the complexation behavior, the IR spectra were recorded for the prepared hydrazone Schiff base ligands and their respective metal complexes.
T92 10466-10527 Sentence denotes The IR Table 1 . coordination to the central metal ion [27] .
T93 10528-10652 Sentence denotes The absence of broad band in the region 2400-3400 cm -1 infers the coordination of carboxylic acid oxygen via deprotonation.
T94 10653-10891 Sentence denotes Further, the strong band due to ν(C=O) of carboxylic acid group has disappeared upon complex formation, since in carboxylate ion the negative charge is equally distributed on two oxygen due to resonance, thereby decreasing the bond order.
T95 10892-10966 Sentence denotes This implies that the carboxylate ion is involved in bond formation [28] .
T96 10967-11181 Sentence denotes Simultaneously, two new bands have appeared in the range of 1520-1580 cm -1 and 1370-1380 cm -1 which are assigned to the asymmetric and symmetric stretching frequencies of coordinated carboxylate ion respectively.
T97 11182-11195 Sentence denotes In Cu(L 1 ) 2
T98 11197-11347 Sentence denotes The 1 H NMR spectrum of ligand 1 (L 1 H, spectrum 5 of supplementary material) shows a broad singlet centered at 12.15 ppm due to amido proton (-NH-).
T99 11348-11461 Sentence denotes Proton attached to carboxylic acid oxygen sometimes due to exchange with moisture in the solvent will not appear.
T100 11462-11544 Sentence denotes The characteristic singlet at 3.87 ppm is due to the resonance of methoxy protons.
T101 11545-11629 Sentence denotes Remaining protons are aromatic and appeared as multiplets between 7.0-9.0 ppm [31] .
T102 11630-11652 Sentence denotes 1 H NMR (400MHz, DMSO-
T103 11654-11944 Sentence denotes Electronic spectra of ligands 1 (L 1 H) and 2 ( respectively, of supplementary material) shows one broad peak due to spin-allowed d-d transition centered at 707 and 717 nm assignable to 2 T 2g 2 E g as is the consequence of distorted octahedral environment around copper (II) ion [36, 37] .
T104 11946-12032 Sentence denotes Thermal behavior of all the metal complexes was studied over a temperature range of 25
T105 12034-12175 Sentence denotes Molar conductance of all the metal complexes was measured at 25 °C by preparing mmol solutions in DMF using the conductivity bridge (G* = 1).
T106 12176-12315 Sentence denotes The values obtained for the complexes not exceeded 20 Ω -1 cm 2 mol -1 which confirms the non-electrolytic nature of metal complexes [39] .
T107 12316-12492 Sentence denotes The molar conductance values have been reproduced in Table 3 along with the elemental analyses data which are in well agreement with the calculated percentages of each element.
T108 12493-12586 Sentence denotes The detailed experimental results of molar conductance study have been tabulated in Table 4 .
T109 12588-12773 Sentence denotes In the present investigation, in vitro MTT cell viability model was taken to study the cytotoxic In case of all tested drugs, dose dependant activity was observed with salient features.
T110 12774-12886 Sentence denotes The IC 50 value of L 1 H, Cu(L 1 ) 2 , Cu(L 2 ) 2 , Ni(L 1 ) 2 and Ni(L 2 ) 2 compounds is found to be less than
T111 12887-12973 Sentence denotes 10µgmL -1 and other tested drugs also demonstrated very promising activity (Table 7) .
T112 12974-13098 Sentence denotes Compared with control group, the cells treated with ligands and metal complexes showed significant detach in culture medium.
T113 13099-13343 Sentence denotes There was a decrease in number of cells as well as observable abnormalities in the treated group of cells such as turgidity, shrunken in shape, cell breakage, cell shrinkage and apoptotic bodies are observed compared to untreated control cells.
T114 13344-13501 Sentence denotes Microscopic examination revealed that morphological changes and shrinkage of cells occurred, leading to cell apoptosis induced by tested compounds [40, 41] .
T115 13502-13664 Sentence denotes IC 50 values of ligands and their respective metal complexes in µgmL -1 for the MCF-7 cell line are compiled in Table 5 . cell line v/s concentration in µgmL -1 .
T116 13666-13782 Sentence denotes Designing small molecules help in targeting specific sites on a DNA strand and can lead to novel therapeutic agents.
T117 13783-13942 Sentence denotes Photocleavage study of DNA also helps in various applications like photodynamic therapy of cancers, DNA foot printing agents and in genomic research [42, 43] .
T118 13943-14058 Sentence denotes Interaction of metal complexes with pBR322 DNA was studied using Agarose gel breaks and smear appearance [44, 45] .
T119 14059-14203 Sentence denotes Overall findings have revealed that the tested compounds can successfully cleave the DNA as it is evident from the images reproduced in Fig. 9 .
T120 14205-14217 Sentence denotes In Table 8 .
T121 14219-14389 Sentence denotes Free radicals lead to the severe causes and implications in the occurrence of various diseases such as liver cirrhosis, atherosclerosis, cancer, diabetes and aging [47] .
T122 14390-14497 Sentence denotes Antioxidants play an important role in the control of free radicals by delaying or inhibiting its activity.
T123 14498-14593 Sentence denotes Table 9 Experimental results of L 1 H and its metal complexes on DPPH radical scavenging model.
T124 14595-14730 Sentence denotes In the current study, two new methoxy and t-butyl substituted hydrazone Schiff base ligands and their metal complexes were synthesized.
T125 14731-14839 Sentence denotes The key precursors, ligands and their transition metal complexes were characterized by spectral ( 1 H and 13