Percorrer por autor "Campos, Joana F."
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- New di(hetero)aryl)ethers and Di(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, growth inhibitory activity on tumor cell lines and non tumor cells, effects on cell cycle and on apoptosisPublication . Queiroz, Maria João R.P.; Peixoto, Daniela; Calhelha, Ricardo C.; Soares, Pedro; Santos, Tiago; Lima, Raquel T.; Campos, Joana F.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaThe thienopyridine skeleton has been reported as having interesting biological activities namely antitumor[1,2] antiangiogenic.[3A] New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing 7-position of the thieno[3,2-bJpyridine, using copper (C-O) or palladium (C-N) catalyzed couplings, respectively, of the 7-t>rolmo: thieno[3,2-bJpyridine (1) with ortho, meta and para fluoro or methoxy phenols and anilines.
- New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell deathPublication . Queiroz, Maria João R.P.; Peixoto, Daniela; Calhelha, Ricardo C.; Soares, Pedro; Santos, Tiago; Lima, Raquel T.; Campos, Joana F.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Vasconcelos, M. HelenaNew fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-b]pyridine, using copper (C–O) or palladium (C–N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-b]pyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCT15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI50 concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI50 values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI50 concentrations showing to be the most promising as antitumoral.
- Synthesis and evaluation of the antitumor potential of new aminated or methoxylated di(hetero)arylthioethers in the thieno[3,2-b]pyridine seriesPublication . Calhelha, Ricardo C.; Campos, Joana F.; Peixoto, Daniela; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Queiroz, Maria João R.P.Synthesis and evaluation of the antitumor potential of new aminated or methoxylated di(hetero)arylthioethers in the thieno[3,2-b]pyridine séries. In 1st Symposium on Medicinal Chemistry. Braga Several thienopyridines have already been described as inhibitors of cell proliferation using human tumor cells[1,2], highlighting the interest of studying their antitumorpotential. ln this work, we present the synthesis of di(hetero)arylthioethers 1a-fby SNAr of the 7-chloro thieno[3,2- b]pyridine with amino or methoxy thiophenols in good to high yields, like presented in the scheme.
- Synthesis of new N-[3-(thieno[3,2-b]pyridine-7-ylthio)phenyl]benzamides as potential inhibitors of VEGFR2 using rational designPublication . Queiroz, Maria João R.P.; Begouin, Agathe; Campos, Joana F.; Peixoto, Daniela; Froufe, Hugo J.C.; Calhelha, Ricardo C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) is the major receptor of the angiogenic effects when linked to VEGF released by tumors. It has a well known role as a transmembrane receptor activating multiple signaling pathways of proliferation and migration of endothelial cells [1], thus leading to the formation and the expansion of new blood vessels (vasculogenesis and angiogenesis) towards the tumor [2]. Therefore, several approaches have been developed to inhibit VEGFR activation and signaling [3]. Some thienopyridine derivatives have already been shown to be inhibitors of the tyrosine kinase domain of VEGFR2 preventing its activation [4]. Herein, we describe the synthesis of new N-[3-(thieno[3,2-b]pyridine-7 -ylthio )phenyl]benzamides, suggested by rational design as potential inhibitors of this domain, either through a Cu-catalyzed C-N coupling of a brominated di(hetero)arylthioether thieno[3,2-b]pyridine with benzamides, or through a reaction of an aminated di(hetero )arylthioether thieno[3,2-b ]pyridine with benzoyl chlorides, as presented below. The inhibition of the tyrosine kinase domain of VEGFR2 by the synthesized compounds will be evaluated by enzymatic and biomolecular assays using VEGF-stimulated Human Umbilical Vein Endothelial Cells (HUVECs).
- Synthesis of new N-[3-(thieno[3,2-b]pyridine-7-ylthio)phenyl]benzamides as potential inhibitors the tyrosine kinase domain of VEGFR2Publication . Campos, Joana F.; Begouin, Agathe; Peixoto, Daniela; Froufe, Hugo J.C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Queiroz, Maria João R.P.Angiogenesis, the growth of new vessels from preexisting vasculature, is a critical step in tumor progression [1]. The tyrosine kinase Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) is a crucial mediator in angiogenesis since the VEGF, excreted by the tumor cells, binds to it activating several signaling pathways involved in cell survival and proliferation [2]. Recently thienopyridine derivatives showed to be promising inhibitors of the tyrosine kinase domain of VEGFR2 [3,4]. In this work new N-[3-(thieno[3,2-b]pyridine-7-ylthio)phenyl]benzamides were prepared as potential VEGFR2 inhibitors suggested by rational design, as presented below.
- Virtual screening of thieno[3,2-b]pyridine arylthioether (hetero)aryltriazole derivatives as potential tyrosine kinase VEGFR2 inhibitors.Publication . Calhelha, Ricardo C.; Begouin, Agathe; Campos, Joana F.; Ferreira, Isabel C.F.R.; Queiroz, Maria João R.P.; Abreu, Rui M.V.Recently we presented a series of thieno[3,2-d]pyrimidinc ether I ,3-diaryl ureas with potent VEGFR2 inhibit ion activity. The binding mode was analyzed and the compounds showed a type-11 tyrosine kinase inhibition mode, with the thienopyrimidine moiety forming a Hydrogen Bond (H-bond) with CYS919 residue and the urea moiety forming a H-bonds with key residues G LU885 and ASP I 046 of the kinase domain. In this study, the potential of changing the more widely used urea moiety to a triazole moiety now in thieno[3,2-b)pyridine a rylthioethers, was analyzed. A number of 3D thieno[3.2-b ]pyrid ine arylthioethers (hetero )aryltriazole derivatives (Figure I) were designed and then molecular docking studies, using AutoDock4, were performed against a VEGFR2 crystal.