The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Martin Smiesko - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics and In Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin
Planta Medica, 2016Co-Authors: Evelyn Jähne, Daniela Eigenmann, Veronika Butterweck, Chethan Sampath, Maxime Culot, Roméo Cecchelli, Fabien Gosselet, Fruzsina Walter, Mária Deli, Martin SmieskoAbstract:The indolo[2,1-b]Quinazoline Alkaloid tryptanthrin was previously identified as a potent anti-inflammatory compound with a unique pharmacological profile. It is a potent inhibitor of cyclooxygenase-2, 5-lipooxygenase-catalyzed leukotriene synthesis, and nitric oxide production catalyzed by the inducible nitric oxide synthase. To characterize the pharmacokinetic properties of tryptanthrin, we performed a pilot in vivo study in male Sprague-Dawley rats (2 mg/kg bw i. v.). Moreover, the ability of tryptanthrin to cross the blood-brain barrier was evaluated in three in vitro human and animal blood-brain barrier models. Bioanalytical UPLC-MS/MS methods used were validated according to current international guidelines. A half-life of 40.63 ± 6.66 min and a clearance of 1.00 ± 0.36 L/h/kg were found in the in vivo pharmacokinetic study. In vitro data obtained with the two primary animal blood-brain barrier models showed a good correlation with an immortalized human monoculture blood-brain barrier model (hBMEC cell line), and were indicative of a high blood-brain barrier permeation potential of tryptanthrin. These findings were corroborated by the in silico prediction of blood-brain barrier penetration. P-glycoprotein interaction of tryptanthrin was assessed by calculation of the efflux ratio in bidirectional permeability assays. An efflux ratio below 2 indicated that tryptanthrin is not subjected to active efflux.
Neeraj Kumar - One of the best experts on this subject based on the ideXlab platform.
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Vasicine from Adhatoda vasica as an organocatalyst for metal-free Henry reaction and reductive heterocyclization of o-nitroacylbenzenes
Tetrahedron Letters, 2016Co-Authors: Sushila Sharma, Manoranjan Kumar, Neeraj Kumar, Vinod Bhatt, Onkar S. Nayal, Maheshwar S. Thakur, Bikram Singh, Upendra SharmaAbstract:Vasicine, a Quinazoline Alkaloid, from the leaves of Adhatoda vasica, has been utilized as an efficient catalyst for metal and base free Henry reaction of various aldehydes with nitro alkanes. The method can be used in the synthesis of various β-nitro alcohols under mild reaction conditions without use of hazardous organic solvents and expensive catalysts. Vasicine is also applied successfully for one pot synthesis of 2,1-benzisoxazoles from o-nitroacylbenzenes in good yields under mild conditions.
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Metal-free transfer hydrogenation of nitroarenes in water with vasicine: revelation of organocatalytic facet of an abundant Alkaloid.
The Journal of organic chemistry, 2014Co-Authors: Sushila Sharma, Manoranjan Kumar, Vishal Kumar, Neeraj KumarAbstract:Vasicine, an abundantly available Quinazoline Alkaloid from the leaves of Adhatoda vasica, has been successfully employed for metal- and base-free reduction of nitroarenes to the corresponding anilines in water. The method is chemoselective and tolerates a wide range of reducible functional groups, such as ketones, nitriles, esters, halogens, and heterocyclic rings. Dinitroarenes reduced selectively to the corresponding nitroanilines under the present reaction conditions.
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Metal-Free Transfer Hydrogenation of Nitroarenes in Water with Vasicine: Revelation of Organocatalytic Facet of an Abundant Alkaloid
2014Co-Authors: Sushila Sharma, Manoranjan Kumar, Vishal Kumar, Neeraj KumarAbstract:Vasicine, an abundantly available Quinazoline Alkaloid from the leaves of Adhatoda vasica, has been successfully employed for metal- and base-free reduction of nitroarenes to the corresponding anilines in water. The method is chemoselective and tolerates a wide range of reducible functional groups, such as ketones, nitriles, esters, halogens, and heterocyclic rings. Dinitroarenes reduced selectively to the corresponding nitroanilines under the present reaction conditions
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Vasicine catalyzed direct C–H arylation of unactivated arenes: organocatalytic application of an abundant Alkaloid
Tetrahedron Letters, 2013Co-Authors: Sushila Sharma, Vishal Kumar, M. Kumar, Neeraj KumarAbstract:Vasicine, a Quinazoline Alkaloid isolated from Adhatoda vasica, has been employed as an organocatalyst for direct C–H arylation of unactivated arenes with aryl iodides/bromides without the assistance of any transition metal catalyst. A number of sensitive functional groups such as methyl, methoxy, O-benzyl, acetyl, and amino were well tolerated under present reaction conditions. Mechanistic investigation supported the involvement of radical intermediates.
Joseph P. Michael - One of the best experts on this subject based on the ideXlab platform.
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Simple indolizidine and quinolizidine Alkaloids.
The Alkaloids. Chemistry and biology, 2015Co-Authors: Joseph P. MichaelAbstract:This review of simple indolizidine and quinolizidine Alkaloids (i.e., those in which the parent bicyclic systems are in general not embedded in polycyclic arrays) is an update of the previous coverage in Volume 55 of this series (2001). The present survey covers the literature from mid-1999 to the end of 2013; and in addition to aspects of the isolation, characterization, and biological activity of the Alkaloids, much emphasis is placed on their total synthesis. A brief introduction to the topic is followed by an overview of relevant Alkaloids from fungal and microbial sources, among them slaframine, cyclizidine, Steptomyces metabolites, and the pantocins. The important iminosugar Alkaloids lentiginosine, steviamine, swainsonine, castanospermine, and related hydroxyindolizidines are dealt with in the subsequent section. The fourth and fifth sections cover metabolites from terrestrial plants. Pertinent plant Alkaloids bearing alkyl, functionalized alkyl or alkenyl substituents include dendroprimine, anibamine, simple Alkaloids belonging to the genera Prosopis, Elaeocarpus, Lycopodium, and Poranthera, and bicyclic Alkaloids of the lupin family. Plant Alkaloids bearing aryl or heteroaryl substituents include ipalbidine and analogs, secophenanthroindolizidine and secophenanthroquinolizidine Alkaloids (among them septicine, julandine, and analogs), ficuseptine, lasubines, and other simple quinolizidines of the Lythraceae, the simple furyl-substituted Nuphar Alkaloids, and a mixed quinolizidine-Quinazoline Alkaloid. The penultimate section of the review deals with the sizable group of simple indolizidine and quinolizidine Alkaloids isolated from, or detected in, ants, mites, and terrestrial amphibians, and includes an overview of the "dietary hypothesis" for the origin of the amphibian metabolites. The final section surveys relevant Alkaloids from marine sources, and includes clathryimines and analogs, stellettamides, the clavepictines and pictamine, and bis(quinolizidine) Alkaloids.
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rings, see: Boeyens (1978). Experimental Crystal data
2012Co-Authors: Daniel P. Pienaar, Sanaz Khorasani, Charles B. De Koning, Joseph P. Michael, Mo K RadiationAbstract:R factor = 0.042; wR factor = 0.124; data-to-parameter ratio = 18.3. The title compound, C13H17NO3, adopts a conformation in which the aromatic ring and the mean plane of the piperidine ring are almost perpendicular to each other [dihedral angle = 79.25 (6)]. The presence of the carbonyl group alters the conformation of the piperidine ring from a chair to a twisted half-chair conformation. In the crystal, pairs of strong O— H O hydrogen bonds link the molecules into inversion dimers. Weak C—H O interactions extend the hydrogen-bonding network into three dimensions. Related literature For the use of related lactams in the synthesis of febrifugine analogues, see: Michael et al. (2006). For information on the biological activity of febrifugine, a Quinazoline Alkaloid with potent antimalarial activity, see: Murata et al. (1998). For the use of chiral oxaziridines in asymmetric hydroxylation, see: Davis et al. (1990). For the conformation of six-membere
Sushila Sharma - One of the best experts on this subject based on the ideXlab platform.
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Vasicine from Adhatoda vasica as an organocatalyst for metal-free Henry reaction and reductive heterocyclization of o-nitroacylbenzenes
Tetrahedron Letters, 2016Co-Authors: Sushila Sharma, Manoranjan Kumar, Neeraj Kumar, Vinod Bhatt, Onkar S. Nayal, Maheshwar S. Thakur, Bikram Singh, Upendra SharmaAbstract:Vasicine, a Quinazoline Alkaloid, from the leaves of Adhatoda vasica, has been utilized as an efficient catalyst for metal and base free Henry reaction of various aldehydes with nitro alkanes. The method can be used in the synthesis of various β-nitro alcohols under mild reaction conditions without use of hazardous organic solvents and expensive catalysts. Vasicine is also applied successfully for one pot synthesis of 2,1-benzisoxazoles from o-nitroacylbenzenes in good yields under mild conditions.
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Metal-free transfer hydrogenation of nitroarenes in water with vasicine: revelation of organocatalytic facet of an abundant Alkaloid.
The Journal of organic chemistry, 2014Co-Authors: Sushila Sharma, Manoranjan Kumar, Vishal Kumar, Neeraj KumarAbstract:Vasicine, an abundantly available Quinazoline Alkaloid from the leaves of Adhatoda vasica, has been successfully employed for metal- and base-free reduction of nitroarenes to the corresponding anilines in water. The method is chemoselective and tolerates a wide range of reducible functional groups, such as ketones, nitriles, esters, halogens, and heterocyclic rings. Dinitroarenes reduced selectively to the corresponding nitroanilines under the present reaction conditions.
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Metal-Free Transfer Hydrogenation of Nitroarenes in Water with Vasicine: Revelation of Organocatalytic Facet of an Abundant Alkaloid
2014Co-Authors: Sushila Sharma, Manoranjan Kumar, Vishal Kumar, Neeraj KumarAbstract:Vasicine, an abundantly available Quinazoline Alkaloid from the leaves of Adhatoda vasica, has been successfully employed for metal- and base-free reduction of nitroarenes to the corresponding anilines in water. The method is chemoselective and tolerates a wide range of reducible functional groups, such as ketones, nitriles, esters, halogens, and heterocyclic rings. Dinitroarenes reduced selectively to the corresponding nitroanilines under the present reaction conditions
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Vasicine catalyzed direct C–H arylation of unactivated arenes: organocatalytic application of an abundant Alkaloid
Tetrahedron Letters, 2013Co-Authors: Sushila Sharma, Vishal Kumar, M. Kumar, Neeraj KumarAbstract:Vasicine, a Quinazoline Alkaloid isolated from Adhatoda vasica, has been employed as an organocatalyst for direct C–H arylation of unactivated arenes with aryl iodides/bromides without the assistance of any transition metal catalyst. A number of sensitive functional groups such as methyl, methoxy, O-benzyl, acetyl, and amino were well tolerated under present reaction conditions. Mechanistic investigation supported the involvement of radical intermediates.
Evelyn Jähne - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics and In Vitro Blood-Brain Barrier Screening of the Plant-Derived Alkaloid Tryptanthrin
Planta Medica, 2016Co-Authors: Evelyn Jähne, Daniela Eigenmann, Veronika Butterweck, Chethan Sampath, Maxime Culot, Roméo Cecchelli, Fabien Gosselet, Fruzsina Walter, Mária Deli, Martin SmieskoAbstract:The indolo[2,1-b]Quinazoline Alkaloid tryptanthrin was previously identified as a potent anti-inflammatory compound with a unique pharmacological profile. It is a potent inhibitor of cyclooxygenase-2, 5-lipooxygenase-catalyzed leukotriene synthesis, and nitric oxide production catalyzed by the inducible nitric oxide synthase. To characterize the pharmacokinetic properties of tryptanthrin, we performed a pilot in vivo study in male Sprague-Dawley rats (2 mg/kg bw i. v.). Moreover, the ability of tryptanthrin to cross the blood-brain barrier was evaluated in three in vitro human and animal blood-brain barrier models. Bioanalytical UPLC-MS/MS methods used were validated according to current international guidelines. A half-life of 40.63 ± 6.66 min and a clearance of 1.00 ± 0.36 L/h/kg were found in the in vivo pharmacokinetic study. In vitro data obtained with the two primary animal blood-brain barrier models showed a good correlation with an immortalized human monoculture blood-brain barrier model (hBMEC cell line), and were indicative of a high blood-brain barrier permeation potential of tryptanthrin. These findings were corroborated by the in silico prediction of blood-brain barrier penetration. P-glycoprotein interaction of tryptanthrin was assessed by calculation of the efflux ratio in bidirectional permeability assays. An efflux ratio below 2 indicated that tryptanthrin is not subjected to active efflux.
