Daniele Marciano - Academia.edu (original) (raw)
Papers by Daniele Marciano
Biochimica Et Biophysica Acta: Molecular Basis Of Disease, Jul 1, 1994
ACS Sensors, Mar 24, 2023
Biochemical and Biophysical Research Communications, Aug 1, 1993
Biochemical and Biophysical Research Communications, Oct 1, 1997
Inhibition of Ras-dependent signaling and of oncogenic Ras function by farnesyl transferase inhib... more Inhibition of Ras-dependent signaling and of oncogenic Ras function by farnesyl transferase inhibitors that block Ras membrane anchorage is limited due to alternative prenylation of Ras. Here we demonstrate that inhibition of the Ras-dependent Raf-1-MAPK (mitogen activated protein kinase) cascade is achieved by S-farnesylthiosalicylic acid (FTS) which affects Ras membrane association but not Ras farnesylation. FTS interferes with the activation of Raf-1 and MAPK and inhibits DNA synthesis in Ras-transformed EJ cells at concentrations similar to those at which it inhibits EJ cell growth (5-25 microM). FTS also inhibits MAPK activity and DNA synthesis stimulated by serum, EGF or thrombin in serum-starved untransformed Rat-1 cells, demonstrating the generality of its effects on Ras-dependent signaling. The effects of FTS on MAPK activity developed relatively rapidly (within 2-6 h) consistent with its rapid effect on Ras membrane anchorage. FTS represents a new class of Ras antagonists that may be useful for the inhibition of various types of oncogenic Ras isoforms independently of their prenylation.
Journal of Medicinal Chemistry, 2019
The effects of the CF 2 H moiety on H-bond acidity and lipophilicity of various compounds, when a... more The effects of the CF 2 H moiety on H-bond acidity and lipophilicity of various compounds, when attached directly to an aromatic ring or to other functions like alkyls, ethers/thioethers or electron withdrawing groups, are discussed. It was found that the CF 2 H group acts as a HB-donor with a strong dependence on the attached functional group (A = 0.035-0.165). Regarding the lipophilicity, the CF 2 H group may acts as a more lipophilic bioisostere of OH but as a similar or less lipophilic bioisostere of SH and CH 3 , respectively, when attached to Ar or alkyl. In addition, the lipophilicity of ethers, sulfoxides and sulfones is dramatically increased upon CH 3 /CF 2 H exchange at the position. Interestingly, this exchange significantly affects not only the polarity and the volume of the solutes but also their HB accepting ability, the main factors influencing log P oct. Accordingly, this study may be helpful in the rational design of drugs containing this moiety. H FG F F lipophilicity (log P) ? H-bond acidity (A) ? strongly depends on FG Example: FG = sulfone: A highest ; log P (CF2H-CH3) largest 15-trans-trans vs. 16 calc = 2.8 D E rel = 0.0 kcal/mole
Chemischer Informationsdienst, 1982
Aus den Zimtsäureestern (I) und dem N‐Oxid (II) lassen sich über die entsprechenden Iminiumsalze ... more Aus den Zimtsäureestern (I) und dem N‐Oxid (II) lassen sich über die entsprechenden Iminiumsalze (IV) sowohl die Oxazine (IIIa)‐(IIIf) als auch die Cyanverbindungen (Va) und (Vb) erhalten.
Drug design and discovery, 1993
Rigid analogs of acetylcholine (ACh) were designed for selective actions at muscarinic receptor s... more Rigid analogs of acetylcholine (ACh) were designed for selective actions at muscarinic receptor subtypes. AF102B, AF125, AF150 and AF151 are such rigid analogs of ACh. Whilst AF125 is an M2 > M1 agonist, AF102B, AF150 and AF151 are centrally active M1 agonists. AF102B has a unique agonistic profile showing, inter alia, only part of the M1 electrophysiology of ACh and unusual binding parameters to mAChRs. AF150 and AF151 are more efficacious agonists than AF102B for M1 AChRs in rat cortex and in CHO cells stably transfected with the m1 AChR subtype. In various animal models for Alzheimer's disease (AD) all three agonists (AF102B, AF150 and AF151), and in particular AF102B, exhibited positive effects on mnemonic processes and a wide safety margin. Such agonists, and especially AF102B, can be considered as a rational treatment strategy in AD. Here we review some current features of these compounds, which may be relevant to a rational treatment strategy in AD. Comparison is made,...
International Journal of Molecular Sciences
Impregnated activated carbons (IACs) used in air filtration gradually lose their efficacy for the... more Impregnated activated carbons (IACs) used in air filtration gradually lose their efficacy for the chemisorption of noxious gases when exposed to humidity due to impregnated metal deactivation. In order to stabilize IACs against aging, and to prolong the filters’ shelf life, inorganic phosphate compounds (phosphoric acid and its three salts, NaHPO4, Na2HPO4, and Na3PO4) were used as anti-aging additives for two different chromium-free IACs impregnated with copper, zinc, molybdenum, and triethylenediamine (TEDA). Phosphoric acid, monosodium, and disodium phosphate were found to be very efficient in inhibiting the aging of IACs over long periods against cyanogen chloride (the test agent) chemisorption, with the latter being the most efficient. However, the efficiency of phosphate as an anti-aging additive was not well correlated with its ability to inhibit the migration of metal impregnants, especially copper, from the interior to the external surface of carbon granules. Unlike organic...
Neuroscience Letters, 1997
Life Sciences, 1997
Human SH-SY5Y neuroblastoma cells have been utilized to investigate the mechanism whereby agonist... more Human SH-SY5Y neuroblastoma cells have been utilized to investigate the mechanism whereby agonist occupancy of muscarinic receptors elicits an increase in the tyrosine phosphorylation of focal adhesion kinase (~125~~~). SH-SY5Y cells express muscarinic cholinergic receptors (mAChRs) of predominantly the m3 subtype, which are robustly coupled to phosphoinositide (PPI) hydrolysis and Ca2+ homeostasis. The addition of oxotremorine-M (0x0-M) resulted in an increased tyrosine phosphorylation of ~125 FAK that was maximal by 10 minutes and persisted for 2 hours. HaIf-maximal phosphorylation of ~125~AK was observed at an oxo-M concentration of approximately 10 PM. OxoM-stimulated ~125~~~ phosphorylation was independent of the production of phospholipase C (PLC)-derived second messengers, integrinextracellular matrix interactions, and cell attachment, but required an intact actin microfilament network m8AChR-mediated ~125 F*K phosphorylation was attenuated by the addition of micromolar concentrations of wortmannin, a putative inhibitor of both phosphatidylinositol (PI) 3'kinase and PI 4'-kinase. Wortmannin inhibited both receptor-stimulated ~125~~~ phosphorylation and PPI hydrolysis with similar IC50 values of approximately 1 PM. These results suggest that although the formation of PLC-derived second messengers is not a prerequisite for p125P*K phosphorylation following mAChR activation, inositol phospholipid turnover may nonetheless play a pivotal role in events that initiate the tyrosine phosphorylation of ~125~~~.
Journal of the American Chemical Society, 1990
Journal of the American Chemical Society, 1990
and (Z)-4-[S-MethyI-2-(l-methylethyl)cyclohexylidene]-2cyclohexen-1-one (14b, Each as Four Diaste... more and (Z)-4-[S-MethyI-2-(l-methylethyl)cyclohexylidene]-2cyclohexen-1-one (14b, Each as Four Diastereomeric Pairs). Similar treatment of 778 mg (5.04 mmol) of (-)-menthone (14), as described for l l b , yielded 1.029 g (4.44 mmol, 88%) of 14b as a colorless oil: bp 105-1
Journal of the American Chemical Society, 1990
... (22) Fahey, R. C.; Newton, GL; Dorian, R.; Kosower, E. M. Anal. (23) Newton, GL; Dorian, R.; ... more ... (22) Fahey, R. C.; Newton, GL; Dorian, R.; Kosower, E. M. Anal. (23) Newton, GL; Dorian, R.; Fahey, RC Anal. Biochem. ... 1987, (26) (a) Matthews, 1. T. WJ Immunol. Methods 1982,51,307-309 Matthews, I. T. W.; Decker, R. S.; Knight, CG Biochem. J. 1981, 611-617. ...
Journal of Neurotrauma, 2007
Ras proteins play a role in receptor-mediated signaling pathways and are activated after traumati... more Ras proteins play a role in receptor-mediated signaling pathways and are activated after traumatic brain injury. S-trans-trans-farnesylthiosalicylic acid (FTS), a synthetic Ras inhibitor, acts primarily on the active, GTP-bound form of Ras and was shown to improve neurobehavioral outcome after closed head injury (CHI) in mice. To gain a better understanding of the neuroprotective mechanism of FTS, we used diffusion-weighted imaging (DWI) in a rat model of CHI. Apparent diffusion coefficients (ADC) and transverse relaxation times (T2) were measured in injured rat brains after treatment with vehicle or FTS (5 mg/kg). Neuroprotection by FTS was also assessed in terms of the neurological severity score. One week after injury, significantly better recovery was observed in the FTS-treated rats than in the controls (p = 0.0191). T2 analysis of the magnetic resonance images revealed no differences between the two groups. In contrast, they differed significantly in ADC, particularly at 24 h post-CHI (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05): in the vehicle-treated rats ADC had decreased to approximately 26% below baseline, whereas it had increased to about 10% above baseline in the FTS-treated rats. As the magnitude of ADC reduction is strongly linked to blood perfusion deficit, these results suggest that the neuroprotective mechanism of FTS might be related to an improvement in cerebral perfusion. We propose that FTS, which is currently being tested in humans for anti-cancer indications, should also be considered as a new strategy for the management of head injury.
Journal of Molecular Medicine, 1999
Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of ... more Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32±0.15 g and 1.08±0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.
Heteroatom Chemistry, 1991
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
FEBS Letters, 1993
High levels of prenylated protein methyltransferase are expressed in the developing rat cerebellu... more High levels of prenylated protein methyltransferase are expressed in the developing rat cerebellum and are responsible for methylation of endogenous G-proteins and 50-52 kDa synaptosomal proteins. Enzyme activity in cerebellar synaptosomes of 3 week postnatal rats is 2-fold higher than that found in adult rat cerebellum. A 10-fold rise in activity occurs at the end of the second and during the third postnatal weeks, followed by a subsequent decline. Expression of the enzymes&amp;#39; substrates follows the same pattern. The high methyltransferase activity in 3-week-old cerebellum coincides with the period of granule cell migration and synaptogenesis, suggesting a regulatory role for the enzyme and its substrates in cerebellar ontogenesis.
Liebigs Annalen der Chemie, 1982
Eingegangen am 5. Marz 1982 Durch Cycloadditionen des aus N-(2-Chlorethyliden)cyclohexylamin-N-ox... more Eingegangen am 5. Marz 1982 Durch Cycloadditionen des aus N-(2-Chlorethyliden)cyclohexylamin-N-oxid (2) in Gegenwart von AgBF, in 1,2-Dichlorethan bei 0°C entstehenden reaktiven dipolaren Zwischenproduktes an die Olefine 10af sowie anschlienende Behandlung der regio-und stereoselektiv gebildeten Iminiumsalze l l a-f rnit KCN oder NaBH, in Wasser wurden die substituierten 1 ,tOxazinderivate 12ab bzw. 13a-f erhalten. Bei der Umsetzung von 2 rnit 10 b in Gegenwart von AgBF, in flussigem SO2 als Ldsungsmittel bei-15 "C und anschlieoender Aufarbeitung mit KCN/H,O findet eine Reaktion rnit der Estergruppe der Zimtsaureester (Esterspaltung) statt. Cycloaddition Reactions of N-(2-Chloroethylidene)cyclohexylamine N-Oxide with Cinnamate Derivatives Cycloaddition reactions of N-(2-chloroethylidene)cyclohexylamine N-oxide (2) with the olefins 10a-f at 0°C in the presence of AgBF, in 1,2-dichloroethane as solvent furnish the reactive iminium salts l l a-f in a regio and stereoselective manner. Subsequent reaction of 11 a-f with KCN or NaBH, in water yields the substituted 1,2-oxazine derivatives 12ab and 13af, respectively. Reaction of 10b with 2 in the presence of AgBF, in liquid SO, at-15 "C followed by KCN/H20 work-up causes cleavage of the ester group. Kiirzlich berichteten wir iiber Reaktionen von N-(2-Chlorethyliden)cyclohexylamin-N-oxid (2) rnit elektronenreichen Olefinen, beispielsweise mit 1 ,CDioxenl) (1) sowie (E)-l-Acetoxy-l-propenz) (4) in Gegenwart von Silber-tetrafluoroborat in 1,2-Dichlorethan als Losungsmittel, wobei unter Cycloaddition die Heterocyclen 3 und 5 entstanden.
Chemical Communications, 2013
We report on the first secondary and tertiary complexes of the pillar[5]arene derivative with xen... more We report on the first secondary and tertiary complexes of the pillar[5]arene derivative with xenon in water. We show that the chemical shift of the encapsulated xenon provides information on the type of the formed complex suggesting that has the potential to be used as a platform for NMR biosensors.
Biochimica Et Biophysica Acta: Molecular Basis Of Disease, Jul 1, 1994
ACS Sensors, Mar 24, 2023
Biochemical and Biophysical Research Communications, Aug 1, 1993
Biochemical and Biophysical Research Communications, Oct 1, 1997
Inhibition of Ras-dependent signaling and of oncogenic Ras function by farnesyl transferase inhib... more Inhibition of Ras-dependent signaling and of oncogenic Ras function by farnesyl transferase inhibitors that block Ras membrane anchorage is limited due to alternative prenylation of Ras. Here we demonstrate that inhibition of the Ras-dependent Raf-1-MAPK (mitogen activated protein kinase) cascade is achieved by S-farnesylthiosalicylic acid (FTS) which affects Ras membrane association but not Ras farnesylation. FTS interferes with the activation of Raf-1 and MAPK and inhibits DNA synthesis in Ras-transformed EJ cells at concentrations similar to those at which it inhibits EJ cell growth (5-25 microM). FTS also inhibits MAPK activity and DNA synthesis stimulated by serum, EGF or thrombin in serum-starved untransformed Rat-1 cells, demonstrating the generality of its effects on Ras-dependent signaling. The effects of FTS on MAPK activity developed relatively rapidly (within 2-6 h) consistent with its rapid effect on Ras membrane anchorage. FTS represents a new class of Ras antagonists that may be useful for the inhibition of various types of oncogenic Ras isoforms independently of their prenylation.
Journal of Medicinal Chemistry, 2019
The effects of the CF 2 H moiety on H-bond acidity and lipophilicity of various compounds, when a... more The effects of the CF 2 H moiety on H-bond acidity and lipophilicity of various compounds, when attached directly to an aromatic ring or to other functions like alkyls, ethers/thioethers or electron withdrawing groups, are discussed. It was found that the CF 2 H group acts as a HB-donor with a strong dependence on the attached functional group (A = 0.035-0.165). Regarding the lipophilicity, the CF 2 H group may acts as a more lipophilic bioisostere of OH but as a similar or less lipophilic bioisostere of SH and CH 3 , respectively, when attached to Ar or alkyl. In addition, the lipophilicity of ethers, sulfoxides and sulfones is dramatically increased upon CH 3 /CF 2 H exchange at the position. Interestingly, this exchange significantly affects not only the polarity and the volume of the solutes but also their HB accepting ability, the main factors influencing log P oct. Accordingly, this study may be helpful in the rational design of drugs containing this moiety. H FG F F lipophilicity (log P) ? H-bond acidity (A) ? strongly depends on FG Example: FG = sulfone: A highest ; log P (CF2H-CH3) largest 15-trans-trans vs. 16 calc = 2.8 D E rel = 0.0 kcal/mole
Chemischer Informationsdienst, 1982
Aus den Zimtsäureestern (I) und dem N‐Oxid (II) lassen sich über die entsprechenden Iminiumsalze ... more Aus den Zimtsäureestern (I) und dem N‐Oxid (II) lassen sich über die entsprechenden Iminiumsalze (IV) sowohl die Oxazine (IIIa)‐(IIIf) als auch die Cyanverbindungen (Va) und (Vb) erhalten.
Drug design and discovery, 1993
Rigid analogs of acetylcholine (ACh) were designed for selective actions at muscarinic receptor s... more Rigid analogs of acetylcholine (ACh) were designed for selective actions at muscarinic receptor subtypes. AF102B, AF125, AF150 and AF151 are such rigid analogs of ACh. Whilst AF125 is an M2 > M1 agonist, AF102B, AF150 and AF151 are centrally active M1 agonists. AF102B has a unique agonistic profile showing, inter alia, only part of the M1 electrophysiology of ACh and unusual binding parameters to mAChRs. AF150 and AF151 are more efficacious agonists than AF102B for M1 AChRs in rat cortex and in CHO cells stably transfected with the m1 AChR subtype. In various animal models for Alzheimer's disease (AD) all three agonists (AF102B, AF150 and AF151), and in particular AF102B, exhibited positive effects on mnemonic processes and a wide safety margin. Such agonists, and especially AF102B, can be considered as a rational treatment strategy in AD. Here we review some current features of these compounds, which may be relevant to a rational treatment strategy in AD. Comparison is made,...
International Journal of Molecular Sciences
Impregnated activated carbons (IACs) used in air filtration gradually lose their efficacy for the... more Impregnated activated carbons (IACs) used in air filtration gradually lose their efficacy for the chemisorption of noxious gases when exposed to humidity due to impregnated metal deactivation. In order to stabilize IACs against aging, and to prolong the filters’ shelf life, inorganic phosphate compounds (phosphoric acid and its three salts, NaHPO4, Na2HPO4, and Na3PO4) were used as anti-aging additives for two different chromium-free IACs impregnated with copper, zinc, molybdenum, and triethylenediamine (TEDA). Phosphoric acid, monosodium, and disodium phosphate were found to be very efficient in inhibiting the aging of IACs over long periods against cyanogen chloride (the test agent) chemisorption, with the latter being the most efficient. However, the efficiency of phosphate as an anti-aging additive was not well correlated with its ability to inhibit the migration of metal impregnants, especially copper, from the interior to the external surface of carbon granules. Unlike organic...
Neuroscience Letters, 1997
Life Sciences, 1997
Human SH-SY5Y neuroblastoma cells have been utilized to investigate the mechanism whereby agonist... more Human SH-SY5Y neuroblastoma cells have been utilized to investigate the mechanism whereby agonist occupancy of muscarinic receptors elicits an increase in the tyrosine phosphorylation of focal adhesion kinase (~125~~~). SH-SY5Y cells express muscarinic cholinergic receptors (mAChRs) of predominantly the m3 subtype, which are robustly coupled to phosphoinositide (PPI) hydrolysis and Ca2+ homeostasis. The addition of oxotremorine-M (0x0-M) resulted in an increased tyrosine phosphorylation of ~125 FAK that was maximal by 10 minutes and persisted for 2 hours. HaIf-maximal phosphorylation of ~125~AK was observed at an oxo-M concentration of approximately 10 PM. OxoM-stimulated ~125~~~ phosphorylation was independent of the production of phospholipase C (PLC)-derived second messengers, integrinextracellular matrix interactions, and cell attachment, but required an intact actin microfilament network m8AChR-mediated ~125 F*K phosphorylation was attenuated by the addition of micromolar concentrations of wortmannin, a putative inhibitor of both phosphatidylinositol (PI) 3'kinase and PI 4'-kinase. Wortmannin inhibited both receptor-stimulated ~125~~~ phosphorylation and PPI hydrolysis with similar IC50 values of approximately 1 PM. These results suggest that although the formation of PLC-derived second messengers is not a prerequisite for p125P*K phosphorylation following mAChR activation, inositol phospholipid turnover may nonetheless play a pivotal role in events that initiate the tyrosine phosphorylation of ~125~~~.
Journal of the American Chemical Society, 1990
Journal of the American Chemical Society, 1990
and (Z)-4-[S-MethyI-2-(l-methylethyl)cyclohexylidene]-2cyclohexen-1-one (14b, Each as Four Diaste... more and (Z)-4-[S-MethyI-2-(l-methylethyl)cyclohexylidene]-2cyclohexen-1-one (14b, Each as Four Diastereomeric Pairs). Similar treatment of 778 mg (5.04 mmol) of (-)-menthone (14), as described for l l b , yielded 1.029 g (4.44 mmol, 88%) of 14b as a colorless oil: bp 105-1
Journal of the American Chemical Society, 1990
... (22) Fahey, R. C.; Newton, GL; Dorian, R.; Kosower, E. M. Anal. (23) Newton, GL; Dorian, R.; ... more ... (22) Fahey, R. C.; Newton, GL; Dorian, R.; Kosower, E. M. Anal. (23) Newton, GL; Dorian, R.; Fahey, RC Anal. Biochem. ... 1987, (26) (a) Matthews, 1. T. WJ Immunol. Methods 1982,51,307-309 Matthews, I. T. W.; Decker, R. S.; Knight, CG Biochem. J. 1981, 611-617. ...
Journal of Neurotrauma, 2007
Ras proteins play a role in receptor-mediated signaling pathways and are activated after traumati... more Ras proteins play a role in receptor-mediated signaling pathways and are activated after traumatic brain injury. S-trans-trans-farnesylthiosalicylic acid (FTS), a synthetic Ras inhibitor, acts primarily on the active, GTP-bound form of Ras and was shown to improve neurobehavioral outcome after closed head injury (CHI) in mice. To gain a better understanding of the neuroprotective mechanism of FTS, we used diffusion-weighted imaging (DWI) in a rat model of CHI. Apparent diffusion coefficients (ADC) and transverse relaxation times (T2) were measured in injured rat brains after treatment with vehicle or FTS (5 mg/kg). Neuroprotection by FTS was also assessed in terms of the neurological severity score. One week after injury, significantly better recovery was observed in the FTS-treated rats than in the controls (p = 0.0191). T2 analysis of the magnetic resonance images revealed no differences between the two groups. In contrast, they differed significantly in ADC, particularly at 24 h post-CHI (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05): in the vehicle-treated rats ADC had decreased to approximately 26% below baseline, whereas it had increased to about 10% above baseline in the FTS-treated rats. As the magnitude of ADC reduction is strongly linked to blood perfusion deficit, these results suggest that the neuroprotective mechanism of FTS might be related to an improvement in cerebral perfusion. We propose that FTS, which is currently being tested in humans for anti-cancer indications, should also be considered as a new strategy for the management of head injury.
Journal of Molecular Medicine, 1999
Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of ... more Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32±0.15 g and 1.08±0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.
Heteroatom Chemistry, 1991
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
FEBS Letters, 1993
High levels of prenylated protein methyltransferase are expressed in the developing rat cerebellu... more High levels of prenylated protein methyltransferase are expressed in the developing rat cerebellum and are responsible for methylation of endogenous G-proteins and 50-52 kDa synaptosomal proteins. Enzyme activity in cerebellar synaptosomes of 3 week postnatal rats is 2-fold higher than that found in adult rat cerebellum. A 10-fold rise in activity occurs at the end of the second and during the third postnatal weeks, followed by a subsequent decline. Expression of the enzymes&amp;#39; substrates follows the same pattern. The high methyltransferase activity in 3-week-old cerebellum coincides with the period of granule cell migration and synaptogenesis, suggesting a regulatory role for the enzyme and its substrates in cerebellar ontogenesis.
Liebigs Annalen der Chemie, 1982
Eingegangen am 5. Marz 1982 Durch Cycloadditionen des aus N-(2-Chlorethyliden)cyclohexylamin-N-ox... more Eingegangen am 5. Marz 1982 Durch Cycloadditionen des aus N-(2-Chlorethyliden)cyclohexylamin-N-oxid (2) in Gegenwart von AgBF, in 1,2-Dichlorethan bei 0°C entstehenden reaktiven dipolaren Zwischenproduktes an die Olefine 10af sowie anschlienende Behandlung der regio-und stereoselektiv gebildeten Iminiumsalze l l a-f rnit KCN oder NaBH, in Wasser wurden die substituierten 1 ,tOxazinderivate 12ab bzw. 13a-f erhalten. Bei der Umsetzung von 2 rnit 10 b in Gegenwart von AgBF, in flussigem SO2 als Ldsungsmittel bei-15 "C und anschlieoender Aufarbeitung mit KCN/H,O findet eine Reaktion rnit der Estergruppe der Zimtsaureester (Esterspaltung) statt. Cycloaddition Reactions of N-(2-Chloroethylidene)cyclohexylamine N-Oxide with Cinnamate Derivatives Cycloaddition reactions of N-(2-chloroethylidene)cyclohexylamine N-oxide (2) with the olefins 10a-f at 0°C in the presence of AgBF, in 1,2-dichloroethane as solvent furnish the reactive iminium salts l l a-f in a regio and stereoselective manner. Subsequent reaction of 11 a-f with KCN or NaBH, in water yields the substituted 1,2-oxazine derivatives 12ab and 13af, respectively. Reaction of 10b with 2 in the presence of AgBF, in liquid SO, at-15 "C followed by KCN/H20 work-up causes cleavage of the ester group. Kiirzlich berichteten wir iiber Reaktionen von N-(2-Chlorethyliden)cyclohexylamin-N-oxid (2) rnit elektronenreichen Olefinen, beispielsweise mit 1 ,CDioxenl) (1) sowie (E)-l-Acetoxy-l-propenz) (4) in Gegenwart von Silber-tetrafluoroborat in 1,2-Dichlorethan als Losungsmittel, wobei unter Cycloaddition die Heterocyclen 3 und 5 entstanden.
Chemical Communications, 2013
We report on the first secondary and tertiary complexes of the pillar[5]arene derivative with xen... more We report on the first secondary and tertiary complexes of the pillar[5]arene derivative with xenon in water. We show that the chemical shift of the encapsulated xenon provides information on the type of the formed complex suggesting that has the potential to be used as a platform for NMR biosensors.