•T. arjuna bark extract reduces Cu2+→Cu0 effectively under microwave irradiation.•pH and redox potential values corroborate the reduction mechanism of Cu2+ ions.•The formation of CuNPs here is ...confirmed from UV–Vis spectra and XRD analysis.•CuNPs showed higher inhibitory activity for bacteria compared to fungus.•These bio-capped CuNPs showed very good antioxidant property.
Terminalia arjuna (T. arjuna) bark extract is used to reduce Cu2+→Cu0 under microwave irradiation. The formation of copper nanoparticles (CuNPs) is monitored by recording the UV–Vis absorption spectra for surface plasmon resonance (SPR) peak, ∼535nm. The intensity of SPR increased linearly with increasing temperature of the reaction mixture. The formation mechanism of CuNPs is supported by the observed marginal decrease in pH and an increase in solution potential (E) of the reaction mixture. X-ray diffraction (XRD) pattern of the CuNPs agrees with the reported data for Cu metal and the crystallite size is ∼23nm. Fourier transform infrared spectroscopy (FT-IR) and solid-state 13C NMR shows the presence of plant residues on the CuNPs, i.e., in situ bio-capping is possible by this method. Thermo gravimetric (TG) analysis shows the thermal degradation of plant residue and the conversion of Cu to CuO. Field emission electron microscopic (FESEM) image shows uniform spherical particles obtained here. Elemental analysis by energy dispersive X-ray (EDX) analysis confirms the presence of Cu alone, as expected. The in vitro antimicrobial activity is found to be effective for CuNPs dried at RT when compared to CuNPs dried at 70°C. In addition, CuNPs shows very good antioxidant property.
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•Designed and synthesized new 3 cyanopyridine based polymers for PLED applications.•Polymers display good light absorption as well as emission behavior.•Polymers possess wide band gap ...2.59–2.80 eV with good thermal stability.•Their EL maxima range from 469 to 476 nm with blue emission in their PLED devices.
In this work, we report the design of three new cyanopyridine scaffold based polymers, viz. TPy1-3 as potential blue light emitters for PLED applications. The new polymer design comprise, a cyanopyridine core as an electron accepting entity, thiophene as an electron donating unit with different auxiliary donors, viz. phenylene (TPy1), biphenyl (TPy2), and fluorene (TPy3), and have been synthesized, following standard synthetic protocols including Suzuki-cross coupling polymerization reaction. Further, in order to assess all the prerequisites to act as an active emitter, the polymers TPy1-3, were subjected to structural, thermal, linear optical, electrochemical and computational studies. The results revealed that, all the polymers were thermally stable up to 300 ⁰C and their estimated optical band-gaps were found to be 2.59–2.80 eV. Finally, new polymer light emitting diode (PLED) were fabricated by employing the polymers TPy1-3, as active emissive material with a configuration of ITO/PEDOT: PSS/Polymer/Al. Interestingly, all the fabricated devices, exhibited an intense blue electroluminescence at 12 V with low threshold voltages of 4.2–4.8 V, signifying an effective injection of electron in the device.
Resistive switching (RS)‐based random access memory has been envisaged as a viable alternative to existing memory technology due to its nonvolatility, high switching speed, high endurance/retention, ...and considerably low operating voltage. Herein, a new uniform, repetitive, and stable RS phenomenon is demonstrated based on very low‐cost two‐terminal metal–insulator–metal stack fabricated using a highly redox‐active vanadium‐based polyoxometalate (POM) molecular clusters, V10O286−—belonging to polyoxovanadate (POV) family. The RS is observed to be unipolar and nonvolatile in nature, and occur at a fairly low operating bias voltage (less than 2 V), making it suitable for low‐power operations. The switching event is attributed to the cycling between formation and rupture of tiny conductive nanofilaments formed due to trapping and detrapping of positively charged ionized oxygen vacancy sites present in the active switching layer of V10O286−. POMs, in their rich abundance, are highly stable early transition‐metal oxide nanosized clusters, capable of storing as well as releasing a large number of electrons. In addition, they can undergo fast and reversible redox reactions (both in solid and liquid electrolyte media) in “stepwise” manner—a property that makes them a promising candidate for ultrafast and multi‐level nonvolatile molecular memory for high‐density data storage. Preliminary investigations on the POV‐based memory cells result in device resistance ratio ≈25, endurance for more than 200 cycles, and stable retention time around 2200 s, in fully open air condition.
Highly redox‐active vanadium‐centric polyoxometalate (POM) clusters are exploited for building ultrafast and nonvolatile molecular memory. POMs are large reservoir of electrons and they can undergo fast reduction–oxidation process through electron delocalization around its molecular cage. The results presented here demonstrate the ability of POMs as an active element to fabricate resistive random‐access memory (RRAM) for high‐density data‐storage applications.
The present study aimed to isolate and characterize chemical compounds from Anthocephalus cadamba Miq. bark and evaluate their anticancer activity by in silico, molecular docking, and in vitro ...studies.
Anthocephalus cadamba is a traditionally used Indian medicinal plant. The anticancer and phytochemical properties of this plant remain unexplored except for a few studies.
The objective of the study was to evaluate the antiproliferative activity of extract and fractions against breast cancer and prostate cancer cell lines and isolate and characterize active compounds from bio-active guided fractions. Moreover, the anticancer activity of isolated compounds against breast and prostate cancer cell lines was also evaluated, in addition to in silico and molecular docking interactions of isolated compounds with VEGFR2 and PDGFRα target proteins.
The compounds were isolated and purified with the help of repeated column chromatography, and spectral techniques, such as 1D, 2D NMR, and GC-MS/MS, were used to identify and elucidate the structure of the compounds. Moreover, prediction of activity spectra for substances, physiochemical properties, bioactivity radar prediction, bioactivity score, natural-product likeness, ADME, and toxicity parameters of isolated compounds (AC-1 to AC-4) was performed through various in-silico databases and servers. To evaluate the docking interaction profile and binding energies of compounds, three docking tools were utilized, such as AutoDock, AutoDock Vina, and iGEMDOCK, against two targets VEGFR2 and PDGFRα. MD simulation was performed through ligand and receptor molecular dynamic server (LARMD).
It was found that the A. cadamba bark chloroform fraction demonstrated a significant inhibitory effect against MDA-MB-231, MCF-7, and PC-3 cells in a dose-time-dependent manner. The bioassay-guided isolation afforded four molecules AC-1 to AC-4 from chloroform fraction. Moreover, the GC-MS/MS profiling identified fourteen new molecules which were not reported earlier from A. cadamba. The in-silico study showed that the isolated compounds (AC-1 to AC-4) followed Lipinski's rule and had good oral bioavailability. While compound AC-4 had positive bioactivity scores except for kinase inhibitor activity. The ADMET profiling revealed that AC-4 was non-toxic and easily absorbed in the human intestine, and transportable in the blood-brain barrier compared to AC-1, AC-2, AC-3, and standard drug doxorubicin. Molecular docking and MD simulation assessment also signified AC-4 anticancer activity with dual inhibitory action against the target proteins VEGFR2 and PDGFRα amongst the studied compounds. The in vitro cell viability assay of isolated compounds demonstrated that AC-1 showed IC50 (μg/mL) value of 34.96 ±3.91, 47.76±3.80 69.1±4.96, AC-2; 68.26±4.22, 54.03±5.14, >100, AC-3; 35.34±4.14, 51.5±51.5, 70.8±5.25 and AC-4; 44.2±3.57, 24.2±2.67, 51.2±2.54 for MDA-MB-231, MCF-7, and PC-3 cancer cell lines, respectively and compared with standard drug doxorubicin. Moreover, fluorescence microscopy confirmed the apoptogenic property of compounds. We also found that AC-4 exhibited significant intracellular ROS production in breast cancer cells, thereby inducing apoptosis and eventually cell death.
In conclusion, A. cadamba afforded four pure molecules AC-1 to AC-4 with the identification of fourteen new compounds. The entire in-silico studies concluded that the AC-4 compound had better oral bioavailability, bioactivity score, and ADMET profile among studied molecules. Molecular docking analysis and MD simulation also supported AC-4 dual inhibitory action against both VEGFR2 and PDGFRα receptors. Moreover, the isolated molecules AC-1, AC-2, AC-3, and AC-4 were found to be active against MDA-MB-231, MCF-7, and PC-3 cancer cells. The molecule AC-4 was found to induce ROS-mediated apoptosis in breast cancer cells. It was found that the anticancer inhibitory potentiality of AC-4 is directed to its molecular stereochemistry which specifically binds to the target proteins of breast cancer cells with no toxicological effect. Therefore, AC-4 is suggested to be an effective aspirant for novel drug design and discovery.
•Use of supercritical carbon dioxide pretreatment for process intensification.•Understanding into effect of pretreatment and reaction parameters.•Comparison of the activity of two different lipases ...with reusability studies.•Optimum pretreatment helps in reducing the reaction time from 24 to 6 h.•Novozyme 435 established to be best form with reusability over 15 cycles.
The esterification reaction of glycerol and caprylic acid catalyzed by immobilized lipase has been investigated in the present work quantifying the intensification benefits based on the use of supercritical carbon dioxide pretreatment. Factors influencing the progress of enzymatic reaction such as the pretreatment conditions, reaction time, reaction temperature, molar ratio of the two reactants, type of enzyme and its loading were varied to establish the effect on the progress of reaction. Optimum conditions for pretreatment using supercritical CO2 were established as time of 1 h, pressure of 100 bars and temperature of 50 °C. Use of pretreatment under optimized conditions resulted in a conversion of free fatty acids to tricaprylin as 97.3% in 6 h of reaction time at 50 °C and molar ratio of 4:1 (caprylic acid: glycerol), which was three times higher as compared to the conventional approach (without any pretreatment) performed under same conditions. Two types of immobilized biocatalysts as Novozyme 435 and Lipozyme RM were used and it was established that Novozyme 435 showed better catalytic activity as compared to Lipozyme RM, though importantly both were active even in the presence of supercritical carbon dioxide used as pretreatment. Reuse of both the enzymes up to 15 cycles with supercritical carbon dioxide pretreatment did not affect the activity significantly. The quality analysis of the synthesized product was performed using various physiochemical tests based on the determination of acid value and peroxide value. Overall, it has been established that use of supercritical carbon dioxide pretreatment was more efficient and enhanced the rate of synthesis of tricaprylin significantly as compared to conventional approach. Understanding into effect of reaction and pretreatment parameters also enabled in maximizing the intensification benefits.
•Synthesis of novel spiroindoline-3,4′-pyrano2,3-cpyrazoles derivatives using MerTEAFeCl4 catalyst in aqueous media.•In vitro cytotoxicity assay of synthesized compounds on Min-6 cells.•Greater ...interaction and affinity of spiroindoline-3,4′-pyrano2,3-cpyrazoles with protein observed in docking study.•Evaluation of drug-likeness study and ‘In silico’ ADMET prediction.
A series of spiroindoline-3,4′-pyrano2,3-cpyrazoles were synthesized by a one-pot four-component reaction of ethyl acetoacetate, hydrazine hydrate, malononitrile, and isatin catalyzed by new polymer-supported ionic liquid (PSIL) catalyst in an aqueous solution at ambient conditions. Newly synthesized compounds were fully characterized by FT-IR, 1H and 13C NMR, and mass spectrometry. The pharmacokinetic properties were screened and followed by molecular docking on COX-2 to check the in silico potency. Cytotoxicity of 5a-j molecules was evaluated against the Min-6 pancreatic cancer cell line. The 5a-j molecules have been found to have a good drugable profile and good binding affinity with the COX-2 enzyme. In addition, the in vitro cytotoxic potential of the synthesized compounds showed promising inhibition potential against cancer cell lines. The most promising compounds, 5e (IC50 11.33) and 5g (IC50 17.30) show the most remarkable cytotoxic activity as compared to other analogues. The results convey that the designed molecules are promising products for level-up biological evaluation.
A series of novel spiroindoline-3,4′-pyrano2,3-cpyrazoles derivatives were synthesized by one-pot four-component reaction of ethyl acetoacetate, hydrazine hydrate, malononitrile and various substituted isatins catalyzed by polymer supported ionic liquid (PSIL) in H2O at ambient temperature condition. Newly synthesized compounds were fully characterized by FT-IR, 1H and 13C NMR and mass spectrometry. Significant advantages of current protocol like easy scale up, reusable catalyst, superior green credentials, mild conditions, excellent yields and no chromatographic separation make them superior than existing methods. The in vitro cytotoxicity studies appreciated the considerable potency of synthesized compounds against pancreatic beta-cell line (Min-6) followed by molecular docking studies, drug-likeness and ADMET evaluation.
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Pancreatic cancer is lethal due to poor prognosis with 5-year survival rate lesser than 5 %. Gemcitabine is currently used to treat pancreatic cancer and development of chemoresistance is a major ...obstacle to overcome pancreatic cancer. Nicotine is a known inducer of drug resistance in pancreatic tumor micro-environment. Present study evaluates chemoresistance triggered by nicotine while treating with gemcitabine and chemosensitization using Embelin. Embelin is a naturally occurring benzoquinone from Embelia ribes possessing therapeutic potency. To develop nicotine-induced chemo-resistance, pancreatic cancer cells PANC-1 and MIA PaCa-2 were continuously treated with nicotine followed by exposure to gemcitabine. Gemcitabine sensitivity assay and immunoblotting was performed to assess the chemo-resistance. Antiproliferative assays such as migration assay, clonogenic assay, Mitochondrial Membrane Potential (MMP) assay, dual staining assay, comet assay, Reactive Oxygen Species (ROS) assay, cell cycle analysis and immunoblotting assays were performed to witness the protein expression involved in chemoresistance and chemosensitization. Epithelial to mesenchymal transition was observed in nicotine induced chemoresistant cells. Gemcitabine sensitivity assay revealed that relative resistance was increased to 6.26 (p < 0.0001) and 6.45 (p < 0.0001) folds in resistant PANC-1 and MIA PaCa-2 compared to parental cells. Protein expression studies confirmed resistance markers like hENT1 and dCK were downregulated with subsequent increase in RRM1 expression in resistant cells. Embelin considerably decreased the cell viability with an IC50 value of 4.03 ± 0.08 μM in resistant PANC-1 and 2.11 ± 0.04 μM in resistant MIA PaCa-2. Cell cycle analysis showed Embelin treatment caused cell cycle arrest at S phase in resistant PANC-1 cells; in resistant MIA PaCa-2 cells there was an escalation in the Sub G1. Embelin upregulated Bax, γH2AX, p53, ERK1/2 and hENT1 expression with concomitant down regulation of Bcl-2 and RRM1. Bioactive molecule embelin, its combination with gemcitabine could provide new vistas to overcome chemo resistance in pancreatic cancer.
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•The study deciphers effects of Nicotine treatment on gemcitabine resistance in pancreatic cancer.•Chemoresistant pancreatic cancer cells showed modulation of gemcitabine resistant markers.•Embelin sensitizes the resistant cells through hENT1/RRM1 signalling.
Three new conjugative polymers Th-Py-1, Th-Py-2 and Th-Py-3, were designed, synthesized and characterized. Their thermal, photophysical, theoretical and electroluminescence studies were carried out.
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•Designed and synthesized new 3 cyanopyridine based polymers for PLED applications.•Polymers display light absorption at 377–397 nm and emission at 432–482 nm.•They possess optical band gap of 2.55–2.64 eV with good thermal stability.•Their EL maxima range is 469–476 nm with blue emission in their PLED devices.•Their fluorescence quantum yield varies in the range of 21–45%.
Herein, we report the design of three new blue light emitting conjugated polymers (Th-Py-1, Th-Py-2 and Th-Py-3), carrying cyanopyridine ring as a strong electron accepting unit and thiophene as well as phenylene vinylene scaffolds with different substituents, as electron donating moieties. The newly designed monomers/polymers were synthesized using well-known synthetic protocols such as cyclocondensation, O-alkylation, Suzuki cross coupling, Wittig and Knoevenagel reactions. They were well-characterized by spectral, thermal, photophysical, electrochemical and gel permeation chromatography (GPC) techniques. Further, they were subjected to theoretical studies using DFT simulations, performed at B3LYP/TZVP level using Turbomole 7.2 V software package. The new polymers were tested in PLED devices (ITO/PEDOT: PSS/Polymer/Al) as emissive materials. Optical studies revealed that, all the polymers displayed light absorption in the range of 377–397 nm and blue light emission in the order of 432–482 nm, respectively. Further, their band-gaps were calculated to be in the order of 2.55–2.64 eV using both optical and electrochemical data. Furthermore, the TGA study indicated that, they possess good thermal stability with onset decomposition temperature, greater than 300 ⁰C under nitrogen atmosphere. Interestingly, use of these polymers in new PLEDs as emissive layers, has shown improved performance when compared to previously reported polymers in similar type of devices. They show blue light emission with a low threshold voltage of 3.5–3.9 V, affirming an efficient electron injection in the diodes.
•Introduction of novel polymer supported MerDABCO-SO3HCl catalyst for the synthesis of pyrazolopyranopyrimidines.•High TON-TOF values.•Reusability of the catalyst for four runs.•Use of water as green ...solvent.•Promising antioxidant and antimicrobial activities of pyrazolopyranopyrimidines.•Greater interaction and affinity of pyrazolopyranopyrimidines with protein observed in docking study.
Sulfonic acid functionalized 1,4-diazabicyclo2.2.2octane supported on Merrifield resin, MerDABCO-SO3HCl catalyst was prepared and explored in one-pot four-component reaction of ethyl acetoacetate, hydrazine hydrate, aryl aldehyde and barbituric acid for the synthesis of pyrazolopyranopyrimidines with excellent yields. The catalyst could be easily recovered and reused for four cycles without significant decrease in catalytic activity. The antimicrobial and invitro antioxidant activities of the synthesized pyrazolopyranopyrimidines were found to be promising and antioxidant activities are supported by molecular docking studies.
Sulfonic acid functionalized 1,4-diazabicyclo2.2.2octane supported on Merrifield resin, MerDABCO-SO3HCl catalyst was prepared and explored in one pot condensation reaction of ethyl acetoacetate, hydrazine hydrate, aryl aldehydes and barbituric acid in aqueous medium for the synthesis of pyrazolopyranopyrimidines. The catalyst could be easily recovered and reused for four cycles without significant decrease in catalytic activity and product yields. The antimicrobial and in-vitro antioxidant activities of the synthesized pyrazolopyranopyrimidines were found to be promising and are supported by molecular docking studies. Display omitted
•Novel Pd-Catalysed 3-methyl Indole based Analogues were synthesised via Suzuki-Miyaura and Buchwald Hartwig coupling.•The synthesized compounds were evaluated in vitro for human pancreatic cancer ...cell inhibition assay on Mia PaCa-2 cell line.•The molecular docking studies on HIF-1α and in silico ADMET studies were performed.•Compound 9d exhibited better cytotoxic effect in the series and could be considered as lead for development as a cytotoxic active compound.
Indole is a most prerogative moiety in the evaluation of anticancer agents for its versatility and bio-diversity. The indole based compounds have been reported by the researchers in the last decade with potent anticancer activities. The coupled indole ring system with other biodynamic moieties is known to increase the bio-efficiency. Hence, a series of 3-methyl-indole-2-pyrindine coupled secondary amines have been synthesized via Suzuki-Miyaura and Buchwald Hartwig coupling. The compounds 9a-e have been docked against Hypoxia-inducible factor 1α (HIF-1α) enzyme to demonstrate the binding interactions with the active site, shown the binding affinity from -7.5 to -8.1 Kcal/mol and disclosed the potentiality of synthesized compounds to bind and inhibits the HIF-1α (Pdb Id: 3KCX) pathway and predicted several in silico ADMET descriptors for the 3-methyl Indole analogues. The molecules were screened for their anti-pancreatic cancer activity and tested against Mia PaCa-2 cell line by MTT assay, revealed that; compound 9d exhibited a greater antiproliferation activity in the series, with IC50 of 73.63±2.05 µM. Our present findings revealed that 9d might be a pursuable lead for further anti-pancreatic cancer studies.
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