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Annette Rompel - One of the best experts on this subject based on the ideXlab platform.
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole li...
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole ligands for binding site recognition and thus their indispensable role for the binding of KP1019.
Bernhard K Keppler - One of the best experts on this subject based on the ideXlab platform.
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole li...
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole ligands for binding site recognition and thus their indispensable role for the binding of KP1019.
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En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[OsIVCl4(Hazole)2]
2015Co-Authors: Gabriel E. Büchel, Michael A Jakupec, Bernhard K Keppler, Iryna N Stepanenko, Michaela Hejl, Vladimir B ArionAbstract:By controlled Anderson type rearrangement reactions complexes of the general formula trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole, 2H-Indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-Indazole tautomer stabilization in trans-[OsIVCl4(2H-Indazole)2] is unprecedented in coordination chemistry of Indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H2ind)[RuIIICl4(Hind)2], where Hind = 1H-Indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[OsIVCl4(Hpz)2] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV–vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported
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en route to osmium analogues of kp1019 synthesis structure spectroscopic properties and antiproliferative activity of trans osivcl4 hazole 2
2011Co-Authors: Gabriel E Buchel, Michael A Jakupec, Bernhard K Keppler, Iryna N Stepanenko, Michaela Hejl, Vladimir B ArionAbstract:By controlled Anderson type rearrangement reactions complexes of the general formula trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole, 2H-Indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-Indazole tautomer stabilization in trans-[OsIVCl4(2H-Indazole)2] is unprecedented in coordination chemistry of Indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H2ind)[RuIIICl4(Hind)2], where Hind = 1H-Indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[OsIVCl4(Hpz)2] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV–vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human ca...
Aleksandar Bijelic - One of the best experts on this subject based on the ideXlab platform.
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole li...
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole ligands for binding site recognition and thus their indispensable role for the binding of KP1019.
Duddu S Sharada - One of the best experts on this subject based on the ideXlab platform.
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c sp2 h functionalization of 2h Indazoles at c3 position via palladium ii catalyzed isocyanide insertion strategy leading to diverse heterocycles
2016Co-Authors: Shinde Vidyacharan, Arumugavel Murugan, Duddu S SharadaAbstract:Herein, we have reported an efficient Pd-catalyzed C–H functionalization of 2H-Indazole at C3-position via an isocyanide insertion strategy for the synthesis of unprecedented benzoxazinoIndazoles, indazoloquinaoxalines and benzoxazinoindazolones for the first time. Our new method provides an operationally simple and versatile route for a selective synthesis of 2-(2H-indazol-2-yl)phenols. Furthermore, we developed a sequential one-pot strategy for the synthesis of benzoxazinoindazolone under metal-oxidant-free conditions. We also achieved the isocyanide insertion between C(sp2)–H and oxygen heteroatom for the first time. The key features of the present protocol are construction of 4 bonds in one-pot, synthesis of new skeletally diverse scaffolds, broad substrate scope, high yields and environmentally benign conditions.
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bf3 oet2 mediated metal free one pot sequential multiple annulation cascade smac synthesis of complex and diverse tetrahydroisoquinoline fused hybrid molecules
2016Co-Authors: Anand H Shinde, Shinde Vidyacharan, Duddu S SharadaAbstract:A highly efficient and distinct BF3·OEt2 mediated metal-free SMAC protocol for the synthesis of complex and diverse hybrid molecules viz. Indazole fused tetrahydroisoquinolinoquinoxalines, and tetrahydroisoquinolinodiazepine has been developed. The transformation is based on sequential cascade processes involving 2H-Indazole formation and deprotection Pictet–Spengler cyclization steps in one-pot fashion. The protocol demonstrates the utility of sequential multiple annulations in a cascade fashion. The present one-pot protocol uses the Solid State Melt Reaction (SSMR) strategy for the synthesis of the intermediate 2H-Indazole. The method is operationally simple and represents a new approach for C–C, three C–N and N–N bond formation with a wide substrate scope.
Sarah Theiner - One of the best experts on this subject based on the ideXlab platform.
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole li...
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x ray structure analysis of indazolium trans tetrachlorobis 1h Indazole ruthenate iii kp1019 bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism
2016Co-Authors: Aleksandar Bijelic, Bernhard K Keppler, Sarah Theiner, Annette RompelAbstract:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-Indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human serum proteins in the transportation and accumulation of ruthenium(III) complexes in tumors. Therefore, the interaction between KP1019 and human serum albumin was investigated by means of X-ray crystallography and inductively coupled plasma mass spectrometry (ICP-MS). The structural data unambiguously reveal the binding of two ruthenium atoms to histidine residues 146 and 242, which are both located within well-known hydrophobic binding pockets of albumin. The ruthenium centers are octahedrally coordinated by solvent molecules revealing the dissociation of both Indazole ligands from the ruthenium-based drug. However, a binding mechanism is proposed indicating the importance of the Indazole ligands for binding site recognition and thus their indispensable role for the binding of KP1019.
