scholarly journals Design, Synthesis, and Evaluation of Near-Infrared Fluorescent Molecules Based on 4H-1-Benzopyran Core

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6986
Author(s):  
Shuting Wang ◽  
Shulei Zhu ◽  
Yawen Tanzeng ◽  
Yuexing Zhang ◽  
Chuchu Li ◽  
...  
Keyword(s):  
Near Infrared ◽  
Fold Increase ◽  
High Viscosity ◽  
Design Synthesis ◽  
Imaging Probes ◽  
Donor Acceptor ◽  
Low Toxicity ◽  
Ethanol System ◽  
Fluorescent Molecules

A series of novel fluorescent 4H-1-benzopyrans was designed and developed as near-infrared fluorescent molecules with a compact donor–acceptor-donor architecture. Spectral intensity of the fluorescent molecules M-1, M-2, M-3 varied significantly with the increasing polarities of solvents, where M-3 showed high viscosity sensitivity in glycerol-ethanol system with a 3-fold increase in emission intensity. Increasing concentrations of compound M-3 to 5% BSA in PBS elicited a 4-fold increase in fluorescence intensity, exhibiting a superior environmental sensitivity. Furthermore, the in vitro cellular uptake behavior and CLSM assay of cancer cell lines demonstrated that M-3 could easily enter the cell nucleus and bind to proteins with low toxicity. Therefore, the synthesized near-infrared fluorescent molecules could provide a new direction for the development of optical imaging probes and potential further drugs.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

scholarly journals Design, Synthesis, and Cytotoxicity Assessment of [64Cu]Cu-NOTA-Terpyridine Platinum Conjugate: A Novel Chemoradiotherapeutic Agent with Flexible Linker

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2154
Author(s):  
Meysam Khosravifarsani ◽  
Samia Ait-Mohand ◽  
Benoit Paquette ◽  
Léon Sanche ◽  
Brigitte Guérin
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Human Fibroblasts ◽  
Fold Increase ◽  
Radiation Energy ◽  
Design Synthesis ◽  
Quadruplex Dna ◽  
Low Energy Electrons ◽  
Normal Human

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [64Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (64Cu). The decay of 64Cu produces numerous low-energy electrons, enabling the 64Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA. Accordingly, the in vitro internalization kinetic and the cytotoxic activity of [64Cu]Cu-NOTA-C3-TP and its derivatives were investigated with colorectal cancer (HCT116) and normal human fibroblast (GM05757) cells. Radiolabeling by 64Cu results in a >55,000-fold increase of cytotoxic potential relative to [NatCu]Cu-NOTA-C3-TP at 72 h post administration, indicating a large additive effect between 64Cu and the TP drug. The internalization and nucleus accumulation of [64Cu]Cu-NOTA-C3-TP in the HCT116 cells were, respectively, 3.1 and 6.0 times higher than that for GM05757 normal human fibroblasts, which is supportive of the higher efficiency of the [64Cu]Cu-NOTA-C3-TP for HCT116 cancer cells. This work presents the first proof-of-concept study showing the potential use of the [64Cu]Cu-NOTA-C3-TP conjugate as a targeted chemoradiotherapeutic agent to treat colorectal cancer.

Abstract 305: Development of an Antidote-Controlled RNA Probe for Molecular Thrombi Imaging

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Kady-Ann Steen-Burrell ◽  
Bethany Powell Gray ◽  
Bruce Sullenger
Keyword(s):  
Near Infrared ◽  
Surgical Complication ◽  
High Specificity ◽  
Fold Increase ◽  
Coagulation Factors ◽  
Fluorescence Signal ◽  
Rna Aptamer ◽  
Suitable Target

Vascular thrombosis is a major underlying factor in many cardiovascular diseases worldwide and is also a major post-surgical complication. Early detection and treatment of thrombi improves outcomes for patients since the responsiveness of thrombi to fibrinolytic treatment decreases with thrombus age. The serine protease thrombin plays a central role in thrombogenesis and remains associated with the thrombus thereby facilitating further activation of coagulation factors and platelets after initial clot formation. Therefore, targeting and imaging clot-bound thrombin may provide a way of distinguishing newly formed thrombi from older, constituted ones. The goal of this study was to determine whether a thrombin-binding RNA aptamer conjugated to a near-infrared fluorophore could detect clot-bound thrombin and if a complementary antidote oligonucleotide could remove clot-bound aptamer thereby creating a subtraction image. The thrombin-binding aptamer conjugate, Tog25t-AF680, was assessed for its in vitro binding capability to newly formed human plasma clots using fluorescence reflectance imaging. In comparison to a labeled non-binding control RNA, we observed a greater than 6-fold increase in near-infrared fluorescence (NIRF) target-to-background ratio (TBR) with Tog25t-AF680. Upon treatment with the antidote oligonucleotide (AO4), we observed an approximately 57% reduction in fluorescence signal after 10 minutes of incubation. Our results suggest that thrombin is a suitable target for imaging newly formed clots and that a RNA aptamer conjugate binds to clot-bound thrombin with high specificity. This thrombin-targeting near-infrared probe has the potential to be used as a diagnostic tool for arterial and venous thrombosis and may further advance our understanding of the role of thrombin in vivo.

scholarly journals Design, Synthesis and In Vitro Investigation of Novel Basic Celastrol Carboxamides as Bio-Inspired Leishmanicidal Agents Endowed with Inhibitory Activity against Leishmania Hsp90

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 56
Author(s):  
Ivan Bassanini ◽  
Silvia Parapini ◽  
Erica E. Ferrandi ◽  
Elena Gabriele ◽  
Nicoletta Basilico ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Design Synthesis ◽  
Vitro Assay ◽  
Design And Synthesis ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
In Vitro Investigation ◽  
Low Toxicity ◽  
Leishmania Amastigotes

The natural triterpene celastrol (CE) is here used as lead compound for the design and synthesis of a panel of eleven CE carboxamides that were tested in vitro for their growth inhibitory activity against Leishmania infantum and L.tropica parasites. Among them, in vitro screening identified four basic CE carboxamides endowed with nanomolar leishmanicidal activity, against both the promastigotes and the intramacrophage Leishmania amastigotes forms. These compounds also showed low toxicity toward two human (HMEC-1 and THP-1) and one murine (BMDM) cell lines. Interestingly, the most selective CE analogue (compound 3) was also endowed with the ability to inhibit the ATPase activity of the Leishmania protein chaperone Hsp90 as demonstrated by the in vitro assay conducted on a purified, full-length recombinant protein. Preliminary investigations by comparing it with the naturally occurring Hsp90 active site inhibitor Geldanamycin (GA) in two different in vitro experiments were performed. These promising results set the basis for a future biochemical investigation of the mode of interaction of celastrol and CE-inspired compounds with Leishmania Hsp90.

Abstract 156: Development of a New Bioactivatable Fluorescent Probe for the Study of the Proteolytic Activities Degrading Apolipoprotein A-I in vitro and in vivo

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Foued Maafi ◽  
Baoqiang Li ◽  
Catherine Gebhard ◽  
Mathieu Brodeur ◽  
Louis Villeneuve ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
Protease Inhibitors ◽  
Near Infrared ◽  
Ex Vivo ◽  
Fold Increase ◽  
High Density Lipoproteins ◽  
Apolipoprotein A ◽  
Proteolytic Activities

Introduction and Objective: The possible benefits of high-density lipoproteins (HDL) against atherosclerosis have been largely attributed to its major protein component, apolipoprotein A-I (apoA-I). However, apoA-I can be degraded by diverse processes, including proteases localized in atherosclerotic plaques, which could reduce the effectiveness of HDL-based therapies. Here we describe the development of a new bioactivatable near-infrared apoA-I-Cy5.5 fluorescent probe and its initial use in the assessment of proteolytic activities that degrade apoA-I in vitro, in vivo and ex vivo. Methods and Results: Fluorescence emission of our probe is quenched by saturation of Cy5.5 fluorophore molecules on the full-length apoA-I protein. In vitro proteolysis of the apoA-I probe showed up to 11-fold increase of near-infrared fluorescence (n=5, P ≤ 0.05). Using this apoA-I-Cy5.5 probe, we were able to quantify proteolytic activities from a wide range of proteases targeting serine (chymase), cysteine (cathepsin S) and metalloproteases (MMP-12). Also, we detected activation of the apoA-I-Cy5.5 probe on aortic cryosections from Ldlr-/--Tg for human apoB atherosclerotic (ATX) mice using an in situ zymography assay and observed that broad-spectrum protease inhibitors protect the probe from protease activities, as shown by decreased fluorescence compared to conditions without protease inhibitors (-54%, n= 6 per group, P ≤ 0.001). In vivo, using a combined Fluorescence Molecular Tomography-Magnetic Resonance imaging system, the injected probe exhibited a trend for increased fluorescence in the aorta when infused in ATX mice compared to C57BL/6J wild-type mice. Ex vivo imaging of these aortas showed a 10-fold increase of fluorescence in ATX (n=5) mice compared to CTL (n=3) mice (P ≤ 0.05). Conclusion: Given the potential importance of HDL functionality in the assessment of cardiovascular risk, this novel protease-activatable apoA-I probe may help to improve HDL-based therapies through better characterization of the alterations of functionality of apoA-I or lipid-poor HDL particles in different pathophysiological settings.

scholarly journals Single-component near-infrared optogenetic systems for gene transcription regulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andrii A. Kaberniuk ◽  
Mikhail Baloban ◽  
Mikhail V. Monakhov ◽  
Daria M. Shcherbakova ◽  
Vladislav V. Verkhusha
Keyword(s):  
Transcription Regulation ◽  
Gene Transcription ◽  
Mammalian Cells ◽  
Near Infrared ◽  
Fold Increase ◽  
Single Component ◽  
Visible Range ◽  
Fluorescent Reporter ◽  
Nir Light

AbstractNear-infrared (NIR) optogenetic systems for transcription regulation are in high demand because NIR light exhibits low phototoxicity, low scattering, and allows combining with probes of visible range. However, available NIR optogenetic systems consist of several protein components of large size and multidomain structure. Here, we engineer single-component NIR systems consisting of evolved photosensory core module of Idiomarina sp. bacterial phytochrome, named iLight, which are smaller and packable in adeno-associated virus. We characterize iLight in vitro and in gene transcription repression in bacterial and gene transcription activation in mammalian cells. Bacterial iLight system shows 115-fold repression of protein production. Comparing to multi-component NIR systems, mammalian iLight system exhibits higher activation of 65-fold in cells and faster 6-fold activation in deep tissues of mice. Neurons transduced with viral-encoded iLight system exhibit 50-fold induction of fluorescent reporter. NIR light-induced neuronal expression of green-light-activatable CheRiff channelrhodopsin causes 20-fold increase of photocurrent and demonstrates efficient spectral multiplexing.

scholarly journals Deep NIR-I Emissive Iridium(III) Complex Bearing D-A Ligand: Synthesis, Photophysical Properties and DFT/TDDFT Calculation

Crystals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1038
Author(s):  
Jia-Yang Jiang ◽  
Zi-Han Xu ◽  
Tang Li ◽  
Da-Hua Cai ◽  
Hui Zhou ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Density Function ◽  
Near Infrared ◽  
Theoretical Calculations ◽  
Photophysical Properties ◽  
Nir Dyes ◽  
Donor Acceptor ◽  
Nir Emission ◽  
Biological Performance

Near-infrared (NIR) phosphorescent iridium(III) complexes have been demonstrated to possess photophysical properties superior to those of traditional NIR dyes. However, the NIR emission wavelength is restricted in the range of 700–800 nm. For realizing deeper NIR emission, a novel type of iridium(III) complex was designed and synthesized in this work. The main ligand of the iridium(III) complex was constructed using a donor-acceptor structure containing benzothiophene as the donor and quinoxaline as the acceptor. The β-diketone derivative was chosen as the auxiliary ligand owing to its symmetrical structure and p-donating character. The complex exhibits deep NIR-I phosphorescence (764 nm in CH2Cl2, 811 nm in aqueous solution) and broad full width at half maximum (108 nm in CH2Cl2, 154 nm in aqueous solution). Theoretical calculations based on the density function and time-dependent density function were carried out to support the experimental data. Moreover, in vitro biological performance of the complex was determined as well. This work supports the possibility that via a systematic transformation between the D and A units, the photophysical performance of NIR emissive iridium(III) complexes can be greatly improved.

Increased Protein Synthesis by Human Platelets during Phagocytosis of Latex Particles in Vitro

1976 ◽  
Vol 35 (02) ◽  
pp. 350-357 ◽  
Author(s):  
Hana Bessler ◽  
Galila Agam ◽  
Meir Djaldetti
Keyword(s):  
Protein Synthesis ◽  
Fold Increase ◽  
Human Platelets ◽  
Polystyrene Latex ◽  
Latex Particles ◽  
The Third ◽  
Platelet Protein ◽  
Dose Dependent ◽  
Phagocytotic Activity

SummaryA three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased.Vincristine (20 μg/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.

Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment

1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  
Keyword(s):  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Ex Vivo ◽  
Fold Increase ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Recombinant Hirudin ◽  
Interindividual Differences ◽  
The Relationship

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

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