The Experts below are selected from a list of 1650 Experts worldwide ranked by ideXlab platform
Zeping Xie - One of the best experts on this subject based on the ideXlab platform.
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Isolation, structure elucidation and racemization of (+)- and (−)-pratensilins A–C: unprecedented spiro Indolinone-naphthofuran alkaloids from a marine Streptomyces sp.
Chemical communications (Cambridge England), 2017Co-Authors: Shumin Zhang, Yang Qin, Lin Guo, Ying Zhang, Feng Lingling, Ling Zhou, Sheng-xiang Yang, Qingshou Yao, Gennaro Pescitelli, Zeping XieAbstract:Three pairs of new enantiomeric alkaloids with an unprecedented spiro Indolinone-naphthofuran skeleton were isolated from a marine Streptomyces sp. The pure enantiomers had a marked difference in the enantiomerization processes for the three compounds. DFT calculations in combination with chemical derivatization were performed to corroborate the racemization process via a keto–enol-type tautomerism.
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isolation structure elucidation and racemization of and pratensilins a c unprecedented spiro Indolinone naphthofuran alkaloids from a marine streptomyces sp
Chemical Communications, 2017Co-Authors: Shumin Zhang, Lin Guo, Ying Zhang, Ling Zhou, Sheng-xiang Yang, Qingshou Yao, Gennaro Pescitelli, Qin Yang, Lingling Feng, Zeping XieAbstract:Three pairs of new enantiomeric alkaloids with an unprecedented spiro Indolinone-naphthofuran skeleton were isolated from a marine Streptomyces sp. The pure enantiomers had a marked difference in the enantiomerization processes for the three compounds. DFT calculations in combination with chemical derivatization were performed to corroborate the racemization process via a keto–enol-type tautomerism.
Mirella Rambaldi - One of the best experts on this subject based on the ideXlab platform.
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2 Indolinone a versatile scaffold for treatment of cancer a patent review 2008 2014
Expert Opinion on Therapeutic Patents, 2016Co-Authors: Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella RambaldiAbstract:ABSTRACTIntroduction: 2-Indolinone is a well-known aromatic heterocyclic organic compound. A lot of work has been done on this bicyclic structure by academic and company researchers to synthesize compounds directed to a plethora of molecular targets in order to discover new drug leads. This review presents up-to-date information in the field of cancer therapy research based on this small building block.Areas covered: The present review gives an account of the recent patent literature (2008–2014) describing the discovery of 2-Indolinone derivatives with selected therapeutic activities. In this period, a large amount of patents were published on this topic. We have limited the analysis to 37 patents on 2-Indolinone derivatives having potential clinical application as chemotherapeutic agents. In this review, the therapeutic applications of 2-Indolinone derivatives for the treatment of cancer reported in international patents have been discussed.Expert opinion: 2-Indolinone is the scaffold of the compounds co...
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2-Indolinone a versatile scaffold for treatment of cancer: a patent review (2008–2014)
Expert opinion on therapeutic patents, 2015Co-Authors: Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella RambaldiAbstract:ABSTRACTIntroduction: 2-Indolinone is a well-known aromatic heterocyclic organic compound. A lot of work has been done on this bicyclic structure by academic and company researchers to synthesize compounds directed to a plethora of molecular targets in order to discover new drug leads. This review presents up-to-date information in the field of cancer therapy research based on this small building block.Areas covered: The present review gives an account of the recent patent literature (2008–2014) describing the discovery of 2-Indolinone derivatives with selected therapeutic activities. In this period, a large amount of patents were published on this topic. We have limited the analysis to 37 patents on 2-Indolinone derivatives having potential clinical application as chemotherapeutic agents. In this review, the therapeutic applications of 2-Indolinone derivatives for the treatment of cancer reported in international patents have been discussed.Expert opinion: 2-Indolinone is the scaffold of the compounds co...
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Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-Indolinones: selectivity against colon tumor cells and effect on cell cycle-related events.
Journal of medicinal chemistry, 2008Co-Authors: Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Silvia Burnelli, Lucilla Varoli, Natalia Calonghi, Concettina CappadoneAbstract:The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-Indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
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Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones and study of their effect on the cell cycle.
Journal of medicinal chemistry, 2005Co-Authors: Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Vida Garaliene, William J. Welsh, Sonia Arora, Giovanna FarruggiaAbstract:This paper reports the synthesis of a new series of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones which were tested as potential antitumor agents at the National Cancer Institute. Two derivatives are now under review by BEC (Biological Evaluation Committee of NCI). To investigate the mechanism of action, the effect on cell cycle progression was studied by monitoring them in colon adenocarcinoma HT-29: both were able to block HT-29 in mitosis. 3-[(2,6-Dimethylimidazo[2,1-b]thiazol-5-yl)methylene]-5-chloro-2-Indolinone was the most active compound.
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Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones.
Anti-cancer drug design, 2001Co-Authors: Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Gianluca Giorgi, Laura Salvini, Vida GaralieneAbstract:The synthesis of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones, analogs of compounds recently published, is described. The EIZ isomerism was studied by means of nuclear Overhauser effect experiments and X-ray crystallography. All the compounds were tested as potential antitumor agents. They were also tested as potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine if the antitumor activity was related to this mechanism of action. The results showed that under certain substitution conditions (5-methoxy group for the indole benzene ring and 2-methyl group for the imidazothiazole system), an interesting antitumor activity was found for some compounds. From the analysis of the antitumor data, 3-[(2,6-dimethylimidazo[2,1-b]-thiazol-5-yl)methylene]-5-methoxy-2-Indolinone was the most active of the whole series.
Matthias Hamburger - One of the best experts on this subject based on the ideXlab platform.
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Caco-2 Permeability Studies and In Vitro hERG Liability Assessment of Tryptanthrin and Indolinone.
Planta medica, 2016Co-Authors: Evelyn Jähne, Daniela Eigenmann, Martin Smiesko, Fahimeh Moradi-afrapoli, Sheela Verjee, Veronika Butterweck, Simon Hebeisen, Timm Hettich, Götz Schlotterbeck, Matthias HamburgerAbstract:Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)Indolinone (Indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 ( 10 µM) and Indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations.
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Development and validation of a LC–MS/MS method for assessment of an anti-inflammatory Indolinone derivative by in vitro blood–brain barrier models
Journal of Pharmaceutical and Biomedical Analysis, 2014Co-Authors: Evelyn Jähne, Daniela Eigenmann, Maxime Culot, Roméo Cecchelli, Fruzsina Walter, Mária Deli, Robin Tremmel, Gert Fricker, Martin Smiesko, Matthias HamburgerAbstract:The compound (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (Indolinone) was identified from lipophilic woad extracts (Isatis tinctoria L., Brassicaceae) as a compound possessing potent histamine release inhibitory and anti-inflammatory properties [1]. To further evaluate the potential of Indolinone in terms of crossing the blood-brain barrier (BBB), we screened the compound in several in vitro cell-based human and animal BBB models. Therefore, we developed a quantitative LC-MS/MS method for the compound in modified Ringer HEPES buffer (RHB) and validated it according to FDA and EMA guidelines [2,3]. The calibration curve of Indolinone in the range between 30.0 and 3000ng/ml was quadratic, and the limit of quantification was 30.0ng/ml. Dilution of samples up to 100-fold did not affect precision and accuracy. The carry-over was within acceptance criteria. Indolinone proved to be stable in RHB for 3h at room temperature (RT), and for three successive freeze/thaw cycles. The processed samples could be stored in the autosampler at 10°C for at least 28h. Moreover, Indolinone was stable for at least 16 days in RHB when stored below -65°C. This validation study demonstrates that our method is specific, selective, precise, accurate, and capable to produce reliable results. In the immortalized human BBB mono-culture model, the apparent permeability coefficient from apical to basolateral (PappA→B), and the Papp from basolateral to apical (PappB→A) were 19.2±0.485×10(-6)cm/s and 21.7±0.326×10(-6)cm/s, respectively. For the primary rat/bovine BBB co-culture model a PappA→B of 27.1±1.67×10(-6)cm/s was determined. In the primary rat BBB triple co-culture model, the PappA→B and the PappB→A were 56.2±3.63×10(-6)cm/s and 34.6±1.41×10(-6)cm/s, respectively. The data obtained with the different models showed good correlation and were indicative of a high BBB permeation potential of Indolinone confirmed by in silico prediction calculations. P-glycoprotein (P-gp) interaction for Indolinone was studied with the aid of a calcein-AM uptake assay, and by calculation of the efflux ratio (ER) from the bidirectional permeability assays. For both bidirectional BBB models an ER below 2 was calculated, indicating that no active mediated transport mechanism is involved for Indolinone. In porcine brain capillary endothelial cells (PBCECs), the calcein-AM uptake assay demonstrated that Indolinone is neither a P-gp substrate nor a P-gp inhibitor and is accumulated into cells at high extent.
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Development and validation of a LC-MS/MS method for assessment of an anti-inflammatory Indolinone derivative by in vitro blood-brain barrier models
Journal of pharmaceutical and biomedical analysis, 2014Co-Authors: Evelyn Jähne, Daniela Eigenmann, Maxime Culot, Roméo Cecchelli, Robin Tremmel, Gert Fricker, Martin Smiesko, Fruzsina R. Walter, Mária A. Deli, Matthias HamburgerAbstract:The compound (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (Indolinone) was identified from lipophilic woad extracts (Isatis tinctoria L., Brassicaceae) as a compound possessing potent histamine release inhibitory and anti-inflammatory properties [1]. To further evaluate the potential of Indolinone in terms of crossing the blood-brain barrier (BBB), we screened the compound in several in vitro cell-based human and animal BBB models. Therefore, we developed a quantitative LC-MS/MS method for the compound in modified Ringer HEPES buffer (RHB) and validated it according to FDA and EMA guidelines [2,3]. The calibration curve of Indolinone in the range between 30.0 and 3000ng/ml was quadratic, and the limit of quantification was 30.0ng/ml. Dilution of samples up to 100-fold did not affect precision and accuracy. The carry-over was within acceptance criteria. Indolinone proved to be stable in RHB for 3h at room temperature (RT), and for three successive freeze/thaw cycles. The processed samples could be stored in the autosampler at 10°C for at least 28h. Moreover, Indolinone was stable for at least 16 days in RHB when stored below -65°C. This validation study demonstrates that our method is specific, selective, precise, accurate, and capable to produce reliable results. In the immortalized human BBB mono-culture model, the apparent permeability coefficient from apical to basolateral (PappA→B), and the Papp from basolateral to apical (PappB→A) were 19.2±0.485×10(-6)cm/s and 21.7±0.326×10(-6)cm/s, respectively. For the primary rat/bovine BBB co-culture model a PappA→B of 27.1±1.67×10(-6)cm/s was determined. In the primary rat BBB triple co-culture model, the PappA→B and the PappB→A were 56.2±3.63×10(-6)cm/s and 34.6±1.41×10(-6)cm/s, respectively. The data obtained with the different models showed good correlation and were indicative of a high BBB permeation potential of Indolinone confirmed by in silico prediction calculations. P-glycoprotein (P-gp) interaction for Indolinone was studied with the aid of a calcein-AM uptake assay, and by calculation of the efflux ratio (ER) from the bidirectional permeability assays. For both bidirectional BBB models an ER below 2 was calculated, indicating that no active mediated transport mechanism is involved for Indolinone. In porcine brain capillary endothelial cells (PBCECs), the calcein-AM uptake assay demonstrated that Indolinone is neither a P-gp substrate nor a P-gp inhibitor and is accumulated into cells at high extent.
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(E,Z)-3-(3',5'-Dimethoxy-4'-hydroxy-benzylidene)-2-Indolinone blocks mast cell degranulation.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2010Co-Authors: Sabine Kiefer, A.c. Mertz, Anna Koryakina, Matthias Hamburger, Peter KüenziAbstract:Abstract (E,Z)-3-(3′,5′-Dimethoxy-4′-hydroxy-benzylidene)-2-Indolinone (Indolinone) is an alkaloid that has been identified as a pharmacologically active compound in extracts of the traditional anti-inflammatory herb Isatis tinctoria. Indolinone has been shown to inhibit compound 48/80-induced mast cell degranulation in vitro. Application of Indolinone to bone marrow derived mast cells showed that it was uniformly distributed in the cytoplasm and that cellular uptake was terminated within minutes. Pre-treatment of IgE-sensitized mast cells with 100 nM Indolinone rendered them insensitive against FcɛRI-receptor dependent degranulation. However, upstream signalling induced by antigen such as activation of PI3-K and MAPK remained unaffected. We conclude that Indolinone blocks mast cell degranulation at the level of granule exocitosis with an IC50 of 54 nm.
Alessandra Locatelli - One of the best experts on this subject based on the ideXlab platform.
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2 Indolinone a versatile scaffold for treatment of cancer a patent review 2008 2014
Expert Opinion on Therapeutic Patents, 2016Co-Authors: Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella RambaldiAbstract:ABSTRACTIntroduction: 2-Indolinone is a well-known aromatic heterocyclic organic compound. A lot of work has been done on this bicyclic structure by academic and company researchers to synthesize compounds directed to a plethora of molecular targets in order to discover new drug leads. This review presents up-to-date information in the field of cancer therapy research based on this small building block.Areas covered: The present review gives an account of the recent patent literature (2008–2014) describing the discovery of 2-Indolinone derivatives with selected therapeutic activities. In this period, a large amount of patents were published on this topic. We have limited the analysis to 37 patents on 2-Indolinone derivatives having potential clinical application as chemotherapeutic agents. In this review, the therapeutic applications of 2-Indolinone derivatives for the treatment of cancer reported in international patents have been discussed.Expert opinion: 2-Indolinone is the scaffold of the compounds co...
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2-Indolinone a versatile scaffold for treatment of cancer: a patent review (2008–2014)
Expert opinion on therapeutic patents, 2015Co-Authors: Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella RambaldiAbstract:ABSTRACTIntroduction: 2-Indolinone is a well-known aromatic heterocyclic organic compound. A lot of work has been done on this bicyclic structure by academic and company researchers to synthesize compounds directed to a plethora of molecular targets in order to discover new drug leads. This review presents up-to-date information in the field of cancer therapy research based on this small building block.Areas covered: The present review gives an account of the recent patent literature (2008–2014) describing the discovery of 2-Indolinone derivatives with selected therapeutic activities. In this period, a large amount of patents were published on this topic. We have limited the analysis to 37 patents on 2-Indolinone derivatives having potential clinical application as chemotherapeutic agents. In this review, the therapeutic applications of 2-Indolinone derivatives for the treatment of cancer reported in international patents have been discussed.Expert opinion: 2-Indolinone is the scaffold of the compounds co...
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Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-Indolinones: selectivity against colon tumor cells and effect on cell cycle-related events.
Journal of medicinal chemistry, 2008Co-Authors: Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Silvia Burnelli, Lucilla Varoli, Natalia Calonghi, Concettina CappadoneAbstract:The synthesis of new 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-Indolinones is reported. The antitumor activity was evaluated according to the protocols available at the National Cancer Institute (NCI), Bethesda, MD. To investigate the mechanism of action of the most potent antitumor agent of this series, its effect on growth of HT-29 colon carcinoma cells was studied. Its ability to inhibit cellular proliferation was mediated by cell cycle arrest at the G2/M phase, accompanied by inhibition of ornithine decarboxylase (ODC), the limiting enzyme of polyamine synthesis, and followed by induction of apoptosis.
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Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones and study of their effect on the cell cycle.
Journal of medicinal chemistry, 2005Co-Authors: Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Vida Garaliene, William J. Welsh, Sonia Arora, Giovanna FarruggiaAbstract:This paper reports the synthesis of a new series of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones which were tested as potential antitumor agents at the National Cancer Institute. Two derivatives are now under review by BEC (Biological Evaluation Committee of NCI). To investigate the mechanism of action, the effect on cell cycle progression was studied by monitoring them in colon adenocarcinoma HT-29: both were able to block HT-29 in mitosis. 3-[(2,6-Dimethylimidazo[2,1-b]thiazol-5-yl)methylene]-5-chloro-2-Indolinone was the most active compound.
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Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones.
Anti-cancer drug design, 2001Co-Authors: Aldo Andreani, Massimiliano Granaiola, Alberto Leoni, Alessandra Locatelli, Rita Morigi, Mirella Rambaldi, Gianluca Giorgi, Laura Salvini, Vida GaralieneAbstract:The synthesis of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-Indolinones, analogs of compounds recently published, is described. The EIZ isomerism was studied by means of nuclear Overhauser effect experiments and X-ray crystallography. All the compounds were tested as potential antitumor agents. They were also tested as potential inhibitors of cyclin-dependent kinase 1 (CDK1), in order to determine if the antitumor activity was related to this mechanism of action. The results showed that under certain substitution conditions (5-methoxy group for the indole benzene ring and 2-methyl group for the imidazothiazole system), an interesting antitumor activity was found for some compounds. From the analysis of the antitumor data, 3-[(2,6-dimethylimidazo[2,1-b]-thiazol-5-yl)methylene]-5-methoxy-2-Indolinone was the most active of the whole series.
Shumin Zhang - One of the best experts on this subject based on the ideXlab platform.
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Isolation, structure elucidation and racemization of (+)- and (−)-pratensilins A–C: unprecedented spiro Indolinone-naphthofuran alkaloids from a marine Streptomyces sp.
Chemical communications (Cambridge England), 2017Co-Authors: Shumin Zhang, Yang Qin, Lin Guo, Ying Zhang, Feng Lingling, Ling Zhou, Sheng-xiang Yang, Qingshou Yao, Gennaro Pescitelli, Zeping XieAbstract:Three pairs of new enantiomeric alkaloids with an unprecedented spiro Indolinone-naphthofuran skeleton were isolated from a marine Streptomyces sp. The pure enantiomers had a marked difference in the enantiomerization processes for the three compounds. DFT calculations in combination with chemical derivatization were performed to corroborate the racemization process via a keto–enol-type tautomerism.
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isolation structure elucidation and racemization of and pratensilins a c unprecedented spiro Indolinone naphthofuran alkaloids from a marine streptomyces sp
Chemical Communications, 2017Co-Authors: Shumin Zhang, Lin Guo, Ying Zhang, Ling Zhou, Sheng-xiang Yang, Qingshou Yao, Gennaro Pescitelli, Qin Yang, Lingling Feng, Zeping XieAbstract:Three pairs of new enantiomeric alkaloids with an unprecedented spiro Indolinone-naphthofuran skeleton were isolated from a marine Streptomyces sp. The pure enantiomers had a marked difference in the enantiomerization processes for the three compounds. DFT calculations in combination with chemical derivatization were performed to corroborate the racemization process via a keto–enol-type tautomerism.
