The Experts below are selected from a list of 477 Experts worldwide ranked by ideXlab platform
Rita Ghosh - One of the best experts on this subject based on the ideXlab platform.
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a375 melanoma cells are sensitized to cisplatin induced toxicity by a synthetic nitro Flavone Derivative 2 4 nitrophenyl 4h chromen 4 one through inhibition of parp1
Molecular Biology Reports, 2021Co-Authors: Anindita Mitra, Rita GhoshAbstract:Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. In this work, we have shown that the nitro-Flavone Derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. The synthetic nitro-Flavone Derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.
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a375 melanoma cells are sensitized to cisplatin induced toxicity by a synthetic nitro Flavone Derivative 2 4 nitrophenyl 4h chromen 4 one through inhibition of parp1
Molecular Biology Reports, 2021Co-Authors: Anindita Mitra, Rita GhoshAbstract:BACKGROUND Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. METHODS AND RESULTS In this work, we have shown that the nitro-Flavone Derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. CONCLUSION The synthetic nitro-Flavone Derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.
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preferential interaction with c myc quadruplex dna mediates the cytotoxic activity of a nitro Flavone Derivative in a375 cells
Journal of Photochemistry and Photobiology, 2021Co-Authors: Anindita Mitra, Sudipta Bhowmik, Rita GhoshAbstract:Abstract G-quadruplex DNAs (G4 DNAs) are emerging as promising anticancer drug targets due to their presence in the promoter regions of different oncogenes. Utilizing different spectroscopic techniques like UV–Vis absorption titration, thermal denaturation, spectrofluorimetric titration, fluorescence displacement assay, Job plot analysis, circular dichroism spectroscopy and also, molecular docking studies, the interaction of a synthetic nitro-Flavone, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), with various G4 DNA structures (c-KIT1, c-KIT2, c-MYC, h-TELO and VEGF) was elucidated. We also investigated the effect of 4NCO on different cancer cell lines. Effect on cell morphology, DNA damage, cell cycle arrest, viability and mode of cell death were evaluated in A375 melanoma cells. Our findings indicated that 4NCO showed preferential binding towards c-MYC promoter G4 to stabilize it with a binding constant (Kb) value of the order of ~105 M−1 and binding stoichiometry of ~1:1. It also showed a unique dual binding mode when bound to c-MYC with a lower binding free energy having multiple strong interactions when compared to the other G4s. In cells, it induced DNA damage resulting in cell cycle arrest at G1/S phase until 24 h, after which, cells strictly underwent apoptosis. It also showed a preferential cytotoxicity towards the A375 melanoma cells. The ability of 4NCO to stabilize the c-MYC G4 to possibly suppress the over-expression of MYC was responsible for inhibition of proliferation of these cells. Hence, these results present a novel finding on the effectiveness of the nitro-Flavone Derivative 4NCO as a potent ligand for c-MYC G4 DNA thereby, providing possibilities of its use in cancer therapy for regulating the oncogene expression in cancer cells.
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insight into the binding of a synthetic nitro Flavone Derivative with human poly adp ribose polymerase 1
International Journal of Biological Macromolecules, 2019Co-Authors: Anindita Mitra, Ria Biswas, Angshuman Bagchi, Rita GhoshAbstract:Flavones are important bioactive compounds, many of which are effective in cancer therapy for their ability to target enzymes related to DNA repair and cell proliferation. In this report, the interaction of a synthetic nitroFlavone, 2,4-nitrophenylchromen-4-one (4NCO) with human poly (ADP-ribose) polymerase 1 (hPARP1) was investigated to explore its inhibitory action. Its interaction with hPARP1 was compared with that of other inhibitors through molecular docking studies. Further insight into the 4NCO-hPARP1 interaction was obtained from competitive docking and molecular dynamic simulation studies. In silico mutagenesis studies and per-residue interaction energy calculations were carried out. Quantitative Structure Activity Relationship analysis was also performed to calculate its predictive percent inhibitory activity. Our results indicated that 4NCO exhibited competitive mode of binding to hPARP1. It formed a stable interaction with the protein thereby hindering any further molecular interaction to render it inactive with a predictive inhibition of 96%. It also had good ADMET properties and showed best Autodock binding free energy values compared to other known inhibitors. 4NCO showed good hPARP1 inhibitory properties with higher bioavailability and lower probability of getting effluxed. Development of inhibitors against hPARP1 is important for cell proliferative disorders, where 4NCO can be predicted as a potential new drug.
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studies on the interaction of a synthetic nitro Flavone Derivative with dna a multi spectroscopic and molecular docking approach
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2018Co-Authors: A Mitra, Forid Saikh, Jhantu Das, Somnath Ghosh, Rita GhoshAbstract:Abstract Interaction of a ligand with DNA is often the basis of drug action of many molecules. Flavones are important in this regard as their structural features confer them the ability to bind to DNA. 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO) is an important biologically active synthetic Flavone Derivative. We are therefore interested in studying its interaction with DNA. Absorption spectroscopy studies included standard and reverse titration, effect of ionic strength on titration, determination of stoichiometry of binding and thermal denaturation. Spectrofluorimetry techniques included fluorimetric titration, quenching studies and fluorescence displacement assay. Assessment of relative viscosity and estimation of thermodynamic parameters from CD spectral studies were also undertaken. Furthermore, molecular docking analyses were also done with different short DNA sequences. The fluorescent Flavone 4NCO reversibly interacted with DNA through partial intercalation as well as minor-groove binding. The binding constant and the number of binding sites were of the order 104 M−1 and 1 respectively. The binding stoichiometry with DNA was found to be 1:1. The nature of the interaction of 4NCO with DNA was hydrophobic in nature and the process of binding was spontaneous, endothermic and entropy-driven. The Flavone also showed a preference for binding to GC rich sequences. The study presents a profile for structural and thermodynamic parameters, for the binding of 4NCO with DNA. DNA is an important target for ligands that are effective against cell proliferative disorders. In this regard, the molecule 4NCO is important since it can exert its biological activity through its DNA binding ability and can be a potential drug candidate.
Anindita Mitra - One of the best experts on this subject based on the ideXlab platform.
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a375 melanoma cells are sensitized to cisplatin induced toxicity by a synthetic nitro Flavone Derivative 2 4 nitrophenyl 4h chromen 4 one through inhibition of parp1
Molecular Biology Reports, 2021Co-Authors: Anindita Mitra, Rita GhoshAbstract:Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. In this work, we have shown that the nitro-Flavone Derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. The synthetic nitro-Flavone Derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.
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a375 melanoma cells are sensitized to cisplatin induced toxicity by a synthetic nitro Flavone Derivative 2 4 nitrophenyl 4h chromen 4 one through inhibition of parp1
Molecular Biology Reports, 2021Co-Authors: Anindita Mitra, Rita GhoshAbstract:BACKGROUND Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. METHODS AND RESULTS In this work, we have shown that the nitro-Flavone Derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. CONCLUSION The synthetic nitro-Flavone Derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.
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preferential interaction with c myc quadruplex dna mediates the cytotoxic activity of a nitro Flavone Derivative in a375 cells
Journal of Photochemistry and Photobiology, 2021Co-Authors: Anindita Mitra, Sudipta Bhowmik, Rita GhoshAbstract:Abstract G-quadruplex DNAs (G4 DNAs) are emerging as promising anticancer drug targets due to their presence in the promoter regions of different oncogenes. Utilizing different spectroscopic techniques like UV–Vis absorption titration, thermal denaturation, spectrofluorimetric titration, fluorescence displacement assay, Job plot analysis, circular dichroism spectroscopy and also, molecular docking studies, the interaction of a synthetic nitro-Flavone, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), with various G4 DNA structures (c-KIT1, c-KIT2, c-MYC, h-TELO and VEGF) was elucidated. We also investigated the effect of 4NCO on different cancer cell lines. Effect on cell morphology, DNA damage, cell cycle arrest, viability and mode of cell death were evaluated in A375 melanoma cells. Our findings indicated that 4NCO showed preferential binding towards c-MYC promoter G4 to stabilize it with a binding constant (Kb) value of the order of ~105 M−1 and binding stoichiometry of ~1:1. It also showed a unique dual binding mode when bound to c-MYC with a lower binding free energy having multiple strong interactions when compared to the other G4s. In cells, it induced DNA damage resulting in cell cycle arrest at G1/S phase until 24 h, after which, cells strictly underwent apoptosis. It also showed a preferential cytotoxicity towards the A375 melanoma cells. The ability of 4NCO to stabilize the c-MYC G4 to possibly suppress the over-expression of MYC was responsible for inhibition of proliferation of these cells. Hence, these results present a novel finding on the effectiveness of the nitro-Flavone Derivative 4NCO as a potent ligand for c-MYC G4 DNA thereby, providing possibilities of its use in cancer therapy for regulating the oncogene expression in cancer cells.
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insight into the binding of a synthetic nitro Flavone Derivative with human poly adp ribose polymerase 1
International Journal of Biological Macromolecules, 2019Co-Authors: Anindita Mitra, Ria Biswas, Angshuman Bagchi, Rita GhoshAbstract:Flavones are important bioactive compounds, many of which are effective in cancer therapy for their ability to target enzymes related to DNA repair and cell proliferation. In this report, the interaction of a synthetic nitroFlavone, 2,4-nitrophenylchromen-4-one (4NCO) with human poly (ADP-ribose) polymerase 1 (hPARP1) was investigated to explore its inhibitory action. Its interaction with hPARP1 was compared with that of other inhibitors through molecular docking studies. Further insight into the 4NCO-hPARP1 interaction was obtained from competitive docking and molecular dynamic simulation studies. In silico mutagenesis studies and per-residue interaction energy calculations were carried out. Quantitative Structure Activity Relationship analysis was also performed to calculate its predictive percent inhibitory activity. Our results indicated that 4NCO exhibited competitive mode of binding to hPARP1. It formed a stable interaction with the protein thereby hindering any further molecular interaction to render it inactive with a predictive inhibition of 96%. It also had good ADMET properties and showed best Autodock binding free energy values compared to other known inhibitors. 4NCO showed good hPARP1 inhibitory properties with higher bioavailability and lower probability of getting effluxed. Development of inhibitors against hPARP1 is important for cell proliferative disorders, where 4NCO can be predicted as a potential new drug.
Jacques Lalevée - One of the best experts on this subject based on the ideXlab platform.
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3-HydroxyFlavone and N-Phenylglycine in High Performance Photoinitiating Systems for 3D Printing and Photocomposites Synthesis
Macromolecules, 2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:We propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PI) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples (e.g., 3D printing) or composites upon visible light exposure (light-emitting diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (combination Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near-UV light LED@385 nm. Also interestingly, a charge transfer complex (CTC) between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found, and high final reactive function conversions are obtained. T...
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3 hydroxyFlavone and n phenylglycine in high performance photoinitiating systems for 3d printing and photocomposites synthesis
Journal of Material Sciences & Engineering, 2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:In this work, we propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PIs) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples or composites upon visible light exposure (Light-Emitting Diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near UV light LED@385 nm. Also interestingly, a charge transfer complex CTC between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found and high final reactive function conversions are obtained. The use of the new proposed initiating systems as materials for laser write or 3D printing experiments was also especially carried out with the formation of printed green fluorescent photopolymers. This green fluorescence obtained with naturally occurring 3-hydroxyFlavone compound can be ascribed to the excited state intramolecular proton transfer ESIPT character. A full picture of the included photochemical mechanisms is given. Remarkably, 3-hydroxyFlavone is also very efficient for photocomposites synthesis with glass fibers (thick samples with good depth of cure) using UV or LED@395 nm conveyor.
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3-HydroxyFlavone and N-Phenylglycine in High Performance Photoinitiating Systems for 3D Printing and Photocomposites Synthesis
Macromolecules, 2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:We propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PI) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples (e.g., 3D printing) or composites upon visible light exposure (light-emitting diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (combination Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near-UV light LED@385 nm. Also interestingly, a charge transfer complex (CTC) between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found, and high final reactive function conversions are obtained. The use of the new proposed initiating systems as materials for laser write or 3D printing experiments was also especially carried out with the formation of printed green fluorescent photopolymers. This green fluorescence obtained with naturally occurring 3-hydroxyFlavone compound can be ascribed to the excited state intramolecular proton transfer ESIPT character. A full picture of the included photochemical mechanisms is given. Remarkably, the 3-hydroxyFlavone/amino acid system is also very efficient for photocomposites synthesis with glass fibers (thick samples with good depth of cure) using UV or LED@395 nm conveyor.
Sherman F Stinson - One of the best experts on this subject based on the ideXlab platform.
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clinical pharmacology of flavopiridol following a 72 hour continuous infusion
Annals of Pharmacotherapy, 2003Co-Authors: Michelle A Rudek, Sherman F Stinson, Kenneth S Bauer, Richard Lush, Adrian M Senderowicz, Donna Headlee, Susan G Arbuck, Michael C Cox, Anthony J Murgo, Edward A SausvilleAbstract:BackgroundFlavopiridol, a novel Flavone Derivative, inhibits cyclin-dependent kinase-1. We initiated a Phase I trial in patients with refractory solid tumors to determine the maximum tolerated dose and characterize the adverse effect profile.ObjectiveTo characterize the clinical pharmacology of flavopiridol.MethodsSerial plasma samples were collected and analyzed by HPLC using electrochemical detection. The pharmacokinetics were analyzed by noncompartmental analysis. Enterohepatic recirculation was studied by analyzing fecal samples, with an attempt to correlate cholecystokinin and post-infusional peak concentrations. The plasma protein binding was studied using equilibrium dialysis.ResultsSeventy-six patients were treated with flavopiridol at 13 dose levels for a total of 504 cycles of treatment. The average steady-state concentration was 26.5 and 253 nM at 4 and 122.5 mg/m2, respectively. The clearance ranged from 49.9 to 2943 mL/min, with nonlinearity at doses >50 mg/m2/d. A post-infusional increase in...
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flavopiridol induces apoptosis of normal lymphoid cells causes immunosuppression and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts
Blood, 1998Co-Authors: Francisco Arguello, Mark J Alexander, Judith A Sterry, Gabriela Tudor, Erik M Smith, Naina T Kalavar, John F Greene, William Koss, David C Morgan, Sherman F StinsonAbstract:Flavopiridol is a novel semisynthetic Flavone Derivative of the alkaloid rohitukine. Flavopiridol is known to inhibit potently the activity of multiple cyclin-dependent kinases. We have assessed its effects on normal and malignant cells in preclinical animal models of localized and disseminated human hematopoietic neoplasms. Flavopiridol, when administered as daily bolus intravenous (IV) injections, produced selective apoptosis of cells in the thymus, spleen, and lymph nodes, resulting in atrophy of these organs. With the exception of the intestinal crypts, apoptosis or tissue damage was absent in all other organs investigated (kidneys, liver, lungs, bone/bone marrow, muscle, and heart). Flavopiridol had a marked apoptotic effect documented by DNA nick-end labeling, or DNA agarose gels in xenografts of human hematopoietic tumors HL-60, SUDHL-4, and Nalm/6. After treatment with 7.5 mg/kg flavopiridol bolus IV or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts underwent complete regressions, and animals remained disease-free several months after one course of flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days underwent either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay was 73.2%. The acquired immunodeficiency syndrome-associated lymphoma AS283 showed no significant response when flavopiridol was used in advanced s.c. tumors, but when treatment was initiated in early stages, there was a complete regression of the early tumors, and a significant overall growth delay (>84%). When flavopiridol was used in severe combined immunodeficient mice bearing disseminated human acute lymphoblastic leukemia Nalm/6 cells, there was 15-day prolongation in survival (P = .0089). We conclude that flavopiridol greatly influences apoptosis in both normal and malignant hematopoietic tissues. This activity was manifested in our study as a potent antileukemia or antilymphoma effect in human tumor xenografts, which was dose and schedule dependent. These findings provide compelling evidence for the use of flavopiridol in human hematologic malignancies.
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Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts
1998Co-Authors: Francisco Arguello, Judith A Sterry, Gabriela Tudor, Erik M Smith, Naina T Kalavar, John F Greene, William Koss, David C Morgan, Mark Alex, Sherman F StinsonAbstract:Flavopiridol is a novel semisynthetic Flavone Derivative of the alkaloid rohitukine. Flavopiridol is known to inhibit potently the activity of multiple cyclin-dependent kinases. We have assessed its effects on normal and malignant cells in preclinical animal models of localized and disseminated human hematopoietic neoplasms. Flavopiridol, when admin-istered as daily bolus intravenous (IV) injections, produced selective apoptosis of cells in the thymus, spleen, and lymph nodes, resulting in atrophy of these organs. With the excep-tion of the intestinal crypts, apoptosis or tissue damage was absent in all other organs investigated (kidneys, liver, lungs, bone/bone marrow, muscle, and heart). Flavopiridol had a marked apoptotic effect documented by DNA nick-end label-ing, or DNA agarose gels in xenografts of human hematopoi-etic tumors HL-60, SUDHL-4, and Nalm/6. After treatmen
Assi Al Mousawi - One of the best experts on this subject based on the ideXlab platform.
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3-HydroxyFlavone and N-Phenylglycine in High Performance Photoinitiating Systems for 3D Printing and Photocomposites Synthesis
Macromolecules, 2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:We propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PI) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples (e.g., 3D printing) or composites upon visible light exposure (light-emitting diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (combination Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near-UV light LED@385 nm. Also interestingly, a charge transfer complex (CTC) between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found, and high final reactive function conversions are obtained. T...
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3 hydroxyFlavone and n phenylglycine in high performance photoinitiating systems for 3d printing and photocomposites synthesis
Journal of Material Sciences & Engineering, 2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:In this work, we propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PIs) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples or composites upon visible light exposure (Light-Emitting Diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near UV light LED@385 nm. Also interestingly, a charge transfer complex CTC between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found and high final reactive function conversions are obtained. The use of the new proposed initiating systems as materials for laser write or 3D printing experiments was also especially carried out with the formation of printed green fluorescent photopolymers. This green fluorescence obtained with naturally occurring 3-hydroxyFlavone compound can be ascribed to the excited state intramolecular proton transfer ESIPT character. A full picture of the included photochemical mechanisms is given. Remarkably, 3-hydroxyFlavone is also very efficient for photocomposites synthesis with glass fibers (thick samples with good depth of cure) using UV or LED@395 nm conveyor.
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3‑HydroxyFlavone and N‑Phenylglycine in High Performance Photoinitiating Systems for 3D Printing and Photocomposites Synthesis
2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:We propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PI) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples (e.g., 3D printing) or composites upon visible light exposure (light-emitting diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (combination Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near-UV light LED@385 nm. Also interestingly, a charge transfer complex (CTC) between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found, and high final reactive function conversions are obtained. The use of the new proposed initiating systems as materials for laser write or 3D printing experiments was also especially carried out with the formation of printed green fluorescent photopolymers. This green fluorescence obtained with naturally occurring 3-hydroxyFlavone compound can be ascribed to the excited state intramolecular proton transfer ESIPT character. A full picture of the included photochemical mechanisms is given. Remarkably, the 3-hydroxyFlavone/amino acid system is also very efficient for photocomposites synthesis with glass fibers (thick samples with good depth of cure) using UV or LED@395 nm conveyor
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3-HydroxyFlavone and N-Phenylglycine in High Performance Photoinitiating Systems for 3D Printing and Photocomposites Synthesis
Macromolecules, 2018Co-Authors: Assi Al Mousawi, Bernadette Graff, Jean Pierre Fouassier, Patxi Garra, Frédéric Dumur, Joumana Toufaily, Tayssir Hamieh, Michael Schmitt, Jacques LalevéeAbstract:We propose to use 3-hydroxyFlavone as a versatile high performance visible light photoinitiator (PI) in combination with an amino acid (N-phenylglycine) for the free radical polymerization (FRP) of methacrylates in thick samples (e.g., 3D printing) or composites upon visible light exposure (light-emitting diode LED@405 nm or LED@477 nm). The high originality of this approach is the use of safer compounds in photoinitiating systems (combination Flavone Derivative/amino acid). 3-HydroxyFlavone can also be used in three-component systems with an iodonium salt and an amine for the cationic polymerization of epoxides upon exposure to near-UV light LED@385 nm. Also interestingly, a charge transfer complex (CTC) between N-phenylglycine NPG and iodonium salt gives also remarkable initiating performance for free radical polymerization of methacrylates upon mild light irradiation conditions (LED@405 nm). High polymerization initiating abilities are found, and high final reactive function conversions are obtained. The use of the new proposed initiating systems as materials for laser write or 3D printing experiments was also especially carried out with the formation of printed green fluorescent photopolymers. This green fluorescence obtained with naturally occurring 3-hydroxyFlavone compound can be ascribed to the excited state intramolecular proton transfer ESIPT character. A full picture of the included photochemical mechanisms is given. Remarkably, the 3-hydroxyFlavone/amino acid system is also very efficient for photocomposites synthesis with glass fibers (thick samples with good depth of cure) using UV or LED@395 nm conveyor.