Search results for "DISCOVERY"
showing 10 items of 4119 documents
Gold(I) Biscarbene Complexes Derived from Vascular-Disrupting Combretastatin A-4 Address Different Targets and Show Antimetastatic Potential
2014
Gold N-heterocyclic carbene (NHC) complexes are an emerging class of anticancer drugs. We present a series of gold(I) biscarbene complexes with NHC ligands derived from the plant metabolite combretastatin A-4 (CA-4) that retain its vascular-disrupting effect, yet address different cellular and protein targets. Unlike CA-4, these complexes did not interfere with tubulin, but with the actin cytoskeleton of endothelial and cancer cells. For the highly metastatic 518A2 melanoma cell line this effect was accompanied by a marked accumulation of cells in the G1 phase of the cell cycle and a suppression of active prometastatic matrix metalloproteinase-2. Despite these mechanistic differences the co…
Synthesis and biological evaluation of 4-nitro-substituted 1, 3-diaryltriazenes as a novel class of potent antitumor agents
2011
Abstract We describe the synthesis and biological activity of a new class of 1,3-diaryltriazenes, namely 4-nitro-substituted 1,3-diaryltriazenes. Structure–activity relationship analysis reveals that 1,3-diaryltriazenes can be modified from inactive to highly cytotoxic compounds by the introduction of two nitro groups at the para positions of benzene rings and two additional electron-withdrawing groups (bromo, chloro, trifluoromethyl or fluoro substituents) at their ortho position. In order to increase the solubility of the modified compounds, we introduced various acyl groups to their triazene nitrogen. The results of LC-MS/MS analysis showed that N -acyltriazenes can be considered as prod…
Semisynthesis and cytotoxicity of styryl-lactone derivatives.
1999
The cytotoxicity and the cell-cycle action of altholactone (1), goniofufurone (2), and eight altholactone derivatives (5-12), were determined in vitro on L-1210 cells. Semisyntheses and structure-activity relationships of these compounds are described. The results of this study suggest that the cytotoxicity of altholactone (1), 11-nitro-altholactone (8), and 7-chloro-6,7-dihydroaltholactone (10) is due to the accumulation of the cells in the G2 + M phase of the cell cycle.
New complex polycyclic compounds: Synthesis, antiproliferative activity and mechanism of action
2020
Abstract Polycyclic or O-glycoconiugate polycyclic compounds 1a-g were previously tested for their in vitro antiproliferative activity. In this series of compounds, activity increases as log P decreases. Specifically, compounds 1d and 1g showed lower log P values together with the best antiproliferative profiles. With the aim of extending our understanding of the structure–activity relationship (SAR) of this class of compounds, we prepared new polycyclic derivatives 2a-c, which bear on each of the two phenyl rings hydrophilic substituents (OH, SO2NH2 or NHCOCH3). These substituents are able to form hydrogen bonds and to decrease the partition coefficient value as compared with compound 1d. …
Diastereoselective Michael Addition of (S)-Mandelic Acid Enolate to Nitroalkenes. Enantioselective Synthesis of α-Hydroxy-α,β-diaryl-γ-lactams.
2004
Abstract The reaction of the lithium enolate of the ( S , S )- cis -1,3-dioxolan-4-one derived from optically active ( S )-mandelic acid and pivalaldehyde with several aromatic nitroalkenes in the presence of HMPA proceeds readily to give the corresponding Michael adducts in good yields and diastereoselectivities. Reduction of the nitro group with Zn/HCl/EtOH/H 2 O with concomitant intramolecular aminolysis of the acetal moiety leads directly to enantiomerically pure α-hydroxy-α,β-diaryl-γ-lactams.
Interactions of diaryl-polyamines with nucleic acids. Allosteric effects with dinuclear copper complexes
2002
Abstract A series of α,ω-diarylamines with a variable number of ethylenediamine units between terminal naphthylrings shows dramatic affinity changes towards double-stranded nucleic acids, particularly upon complexation with Cu(II) ions. Metal salts alone have under the applied conditions only a negligible effect. The affinity of the metal-free ligands towards nucleic acids shows significant differences to those of the underlying polyamines, with a reversed stabilization of DNA instead of the usually observed preference for RNA. The affinity changes and preliminary NMR studies are in line with intercalation of naphthylrings into the double-stranded nucleic acid, which is hampered by complex …
Mononuclear heterocyclic rearrangements—vi
1974
Publisher Summary This chapter discusses the mononuclear heterocyclic rearrangements. The chapter discusses the ring conversion of type 1→2 characterized by nucleophilic attack from a Z atom on a sp 2 -nitrogen atom with displacement of an atom. On this basis, the known ring conversions are tabulated. Taking into account the reactivities observed in the rearrangements, results are presented for 1,2,4-oxadiazole, isoxazole, and 1,2,5-oxadiazole. The sequence involving an oxime group in the side chain is discussed. The chapter presents several attempts for inducing rearrangements in which the reaction center of the starting ring is an atom other than nitrogen. Rearrangement of arylhydrazones …
Synthesis of a technetium-99m labelledL-tyrosine derivative with thefac-99mTc(I)(CO)3-core using a simple kit-procedure
2004
Summary The synthesis of a novel technetium-99m labelled derivative of l-tyrosine as a potential tumour imaging agent for nuclear medicine diagnosis is reported. The synthesis involved the labelling precursor fac-[ 99m Tc(OH2)(CO)3] + which was synthesized using the commercially available Isolink 1 -labelling kit and the tyrosine derivative O-(N,Nbis(carboxymethyl)aminoethyl)-l-tyrosine trifluoroacetate. The labelled compound O( 99m Tc(I)-tricarbonyl-N,N-bis(carboxymethyl)aminoethyl)-l-tyrosine was obtained in a radiochemical yield of 70–80% within 60 min with a radiochemical purity greater than 98% without any HPLC purification step. Purification was achieved merely by solid phase extracti…
Electrochemical behavior of layered annulenes
1985
Abstract The cyclic voltammetric behavior of a series of dimeric [14] annulenes was examined and compared with the monomer. The data suggest a signigficant degree of interaction between the annulene rings when a three-carbon chain connects them, little or no interaction with an eight-carbon chain, and weak interaction with a four-carbon chain.
13C NMR of carbonyl compounds. 3. Structure and dynamics of protonated enones and dienones
1984
Abstract The unsaturated ketones 1 1 – 10 10 were protonated at low temperatures and studied by dynamic 13C NMR spectroscopy. Four interconverting stereoisomers were detected which differ in their conformation with respect to the CO and CC (enone) single bond.