Search results for "Tubulin"
showing 10 items of 116 documents
Synthesis and Biological Evaluation of α-Tubulin-Binding Pironetin Analogues with Enhanced Lipophilicity
2013
Financial support has been granted to M. C. by the Spanish Ministry of Education and Science (project numbers CTQ2008-02800 and CTQ2011-27560), by the Conselleria d'Empresa, Universitat i Ciencia de la Generalitat Valenciana (ACOMP09/113) and by the BANCAJA-UJI Foundation (P1-1B2002-06, P1-1B-2008-14 and PI-1B2011-37). The biological work has been supported in part by grants from the Spanish Ministry of Education and Science (grant number BIO2010-16351) and from the Comunidad de Madrid (grant number S2010/BMD-2457 BIPEDD2-CM), both to J. F. D. We further thank the Matadero Municipal Vicente de Lucas in Segovia for providing the calf brains, which were the source of tubulin.
Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…
2008
Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
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…
Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
2015
Abstract Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progressi…
Is tubulin the sole antigen recognized by a putative anti-bursicon antibody?
1999
Abstract A 56-kDa polypeptide suspected to be the tanning hormone `bursicon' was analyzed using the monoclonal antibody (mAb) 01C10 of Song and Ma. We studied the beetle Tenebrio molitor, for which data on bursicon have been recently published. After purification by two-dimensional gel electrophoresis of brain proteins, the immunoreactive 56-kDa polypeptide was trypsinated and microsequenced. The obtained sequences revealed a high homology with α- and β-tubulins. In a complementary study, immunoreactive clones were isolated, using the 01C10 mAb, from a library in expression vector obtained from Drosophila melanogaster head cDNAs. Again, the isolated clones were found, after cDNA sequencing,…
Sea urchin neural alpha 2 tubulin gene: isolation and promoter analysis
2004
Abstract Expression of Tα2 gene, during sea urchin Paracentrotus lividus development, is spatially and temporally regulated. In order to characterize this gene, we isolated the relevant genomic sequences and scanned the isolated 5 ′ -flanking region in searching for cis -regulatory elements required for proper expression. Gel mobility shift and footprinting assays, as well as reporter gene (CAT and β-gal) expression assays, were used to address cis -regulatory elements involved in regulation. Here we report that an upstream 5 ′ -flanking fragment of PlTα2 gene drives temporal expression of reporter genes congruent with that of endogenous Tα2 gene. The fragment contains cis -elements able to…
Synthesis and biological evaluation of 2-(3 ',4 ',5 '-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors
2006
2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para-position of the 5-phenyl group showed antiproliferative activity in the order of F=CH(3) > OCH(3)=Br=NO(2) > CF(3)=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of apoptosis.
Tubulin-folding cofactor E deficiency is associated with vascular dysfunction and endoplasmatic reticulum stress of vascular smooth muscle cells
2021
Abstract Introduction Endothelial function assessed via flow mediated dilatation (FMD) has shown to predict risk in individuals with established cardiovascular diseases, whereas its predictive value is uncertain in the setting primary prevention. Purpose The aim of the current work was to discover and evaluate novel mediators of vascular dysfunction in the general population and in conditional knock-out transgenic animal models. Methods In order to identify novel targets that were negatively correlated with FMD and investigate their contribution in vascular function, a Genome Wide Association Study (GWAS) of 5,000 participants was performed and subsequently immune cell-, endothelial- and va…
A FOX Binding Site is Necessary for the Activation of Pl-Tuba1a Gene in the neurogenic domains
2016
All echinoderm larvae possess a nervous system consisting of a ciliary band and associated sensory ganglia (apical, oral and lateral ganglia) that controls swimming and feeding. Neurons of the larval nervous system first appear as neuroblasts in the thickened ectoderm of the animal plate (anterior neuroectoderm, ANE) at the late blastula – early gastrula stage and then also in the ciliary band. The neural differentiation process of sea urchin embryos has been analysed and the Gene Regulatory Network involved in the differentiation processes is extensively studied. We have previously isolated an alpha tubulin family member of the sea urchin Paracentrotus lividus (Pl-Tuba1a, formerly known as…
Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tub…
2020
Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3&prime