Search results for "Alkyl"

Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go.

2003

Since the milestone work of Evans and Scott, demonstrating the replication dependence of alkylation-induced aberrations, and Obe and Natarajan, pointing to the critical role of DNA double-strand breaks (DSBs) as the ultimate trigger of aberrations, the field has grown extensively. A notable example is the identification of DNA methylation lesions provoking chromosome breakage (clastogenic) effects, which made it possible to model clastogenic pathways evoked by genotoxins. Experiments with repair-deficient mutants and transgenic cell lines revealed both O<sup>6</sup>-methylguanine (O<sup>6</sup>MeG) and N- methylpurines as critical lesions. For S<sub>N</sub&g…

Late activation of stress kinases (SAPK/JNK) by genotoxins requires the DNA repair proteins DNA-PKcs and CSB.

2005

Although genotoxic agents are powerful inducers of stress kinases (SAPK/JNK), the contribution of DNA damage itself to this response is unknown. Therefore, SAPK/JNK activation of cells harboring specific defects in DNA damage-recognition mechanisms was studied. Dual phosphorylation of SAPK/JNK by the genotoxin methyl methanesulfonate (MMS) occurred in two waves. The early response (≤2 h after exposure) was similar in cells knockout for ATM, PARP, p53, and CSB or defective in DNA-PKcscompared with wild-type cells. The late response however (≥4 h), was drastically reduced in DNA-PKcsand Cockayne's syndrome B (CSB)-deficient cells. Similar results were obtained with human cells lacking DNA-PKc…

Ras-Related GTPase RhoB Forces Alkylation-Induced Apoptotic Cell Death

2000

rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxic treatments. To address the question of the physiological role of RhoB in cellular defense, cells stably overexpressing wild-type RhoB protein were generated. Overexpression of RhoB renders cells hypersensitive to the killing effect of alkylating agents including antineoplastic drugs but not to UV-light and doxorubicin. As compared to control cells, RhoB overexpressing cells revealed an increase in the frequency of alkylation-induced apoptotic cell death. This indicates that RhoB is involved in modulating apoptotic signaling. Furthermore, overexpression of RhoB resulted in a prolonged transient block to DNA replicat…

The Translesion Polymerase Rev3L in the Tolerance of Alkylating Anticancer Drugs

2009

Temozolomide and fotemustine, representing methylating and chloroethylating agents, respectively, are used in the treatment of glioma and malignant melanoma. Because chemoresistance of these tumors is a common phenomenon, identification of the underlying mechanisms is needed. Here we show that Rev3L, the catalytic subunit of the translesion DNA polymerase zeta, mediates resistance to both temozolomide and fotemustine. Rev3L knockout cells are hypersensitive to both agents. It is remarkable that cells heterozygous for Rev3L showed an intermediate sensitivity. Rev3L is not involved in the tolerance of the toxic O6-methylguanine lesion. However, a possible role of Rev3L in the tolerance of O6-…

Inverted molecular cups: 1-D and 2-D Ag(I) coordination polymers from resorcinarene bis-thiacrowns

2016

Resorcinarene bis-thiacrown hosts 1–3 were prepared and crystallized with silver trifluoroacetate yielding one and two dimensional Ag coordination polymers. The complexation of silver in exo-cavity fashion folds the thiacrown bridges inwards transforming the resorcinarene hosts into inverted molecular cups. The silver cations were coordinated to the resorcinarene ligands and trifluoroacetate anions, which act as monodentate or bidendate bridging ligands between the metal ions. Argentophilic Ag⋯Ag (2.93–3.38 A) interactions supported by two bridging carboxylate anions were found in two of the structures, whereas longer Ag⋯Ag distances were observed if only one anion connected the silver cati…

Mononuclear Perfluoroalkyl-Heterocyclic Complexes of Pd(II): Synthesis, Structural Characterization and Antimicrobial Activity

2020

Two mononuclear Pd(II) complexes [PdCl2(pfptp)] (1) and [PdCl2(pfhtp)] (2), with ligands 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), were synthesized and structurally characterized. The two complexes showed a bidentate coordination of the ligand occurring through N atom of pyridine ring and N4 atom of 1,2,4-triazole. Both complexes showed antimicrobial activity when tested against both Gram-negative and Gram-positive bacterial strains.

2.14 Selected Diastereoselective Reactions: Enolate Alkylation

2012

This chapter discusses processes in which enolates are subjected to reaction with alkylating reagents. In all the processes examined here, at least one of the two reaction components is chiral and the reaction gives rise to one or more diastereomeric compounds. In most cases, the enolate is generated through deprotonation of the corresponding carbonyl precursor with a suitable base, but in several cases, the enolate is generated differently, for example, through Michael addition of a nucleophile to a conjugated carbonyl compound. The various factors that have been found to influence the stereochemical outcome of the alkylation reaction in a measurable way are also discussed. The material ha…

Synthesis of (–)-(S)-Norlaudanosine, (+)-(R)-O,O-Dimethylcoclaurine, and (+)-(R)-Salsolidine by Alkylation of an α-Aminonitrile

2007

A short asymmetric synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinoline alkaloids by deprotonation of an unprotected α-aminonitrile and alkylation of the resulting carbanion followed by spontaneous elimination of HCN and asymmetric reduction is described. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

ChemInform Abstract: A Short Synthesis of Pyridines from Deprotonated α-Aminonitriles by an Alkylation/RCM Sequence.

2016

A short synthesis of pyridines from deprotonated α-aminonitriles by an alkylation/RCM sequence

2016

Abstract α-Aminonitriles can serve as versatile key precursors for the synthesis of nitrogen containing heterocycles. After unsuccessful trials involving the [1,2]-Stevens rearrangement of nitrile-stabilized ammonium ylides, we herein report a simple three-step synthesis of substituted pyridines based on an alkylation/ring-closing metathesis/aromatization sequence.