Synthesis of aminodiarylamines in the thieno[3,2-b]pyridine series and effects on tumor cell growth inhibition, cell cycle and apoptosis

Several series of compounds that include the thienopyridine scaffold have been reported as inhibitors of known cancer therapeutic targets or as inhibitors of cell proliferation in tumor cell lines [1,2]. Our research group has already synthesized several thieno[3,2-b]pyridine derivatives by Pd-catalyzed C-C (Suzuki and Sonogashira) and C-N (Buchwald-Hartwig) couplings and some of them have presented tumor cell growth inhibitory activity in cell lines [3- 5]

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 death

New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-blpyridine, using copper (C-O) or palladium (C N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-blpyridine, 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), HCI15 (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 GI(50) 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 GI(50) 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 GI(50) concentrations showing to be the most promising as antitumoral.The authors would like to thank to the Foundation for the Science and Technology (PCT Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho); to FCT and FEDER-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoral grants attributed to R.C.C. (SFRH/BPD/68344/2010) and R.T.L. (SRH/BPD/68787/2010). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT

Wood anatomy of Mollinedia glabra (Spreng.) Perkins (Monimiaceae) in two Restinga Vegetation Formations at Rio das Ostras, RJ, Brazil

This paper aimed to characterize the anatomical structure of the wood of specimens of Mollinedia glabra (Spreng.) Perkins growing in two contiguous formations of restinga vegetation at Praia Virgem, in the municipality of Rio das Ostras, RJ. Both the Open Palmae (OPS) and the Sandy Strip Closed Shrub (SSCS) formations are found in coastal regions that receive between 1,100 and 1,300 mm of rainfall per year. Sapwood samples were collected in both formations. Typical anatomical features for this species include: solitary vessels, radial multiples or clusters elements, that are circular to angular in outline, 5-15 barred scalarifor perforation plates, ood parenchya scanty, septate fiber-tracheids, and wide multiseriate rays with prismatic crystals. Statistical analyses indicated a significant increase in the frequency of vessel elements and an increase in fiber-tracheid diameters in OPS individuals. These characteristics are considered structural adaptations to increased water needs caused by a greater exposure to sunlight. Continuous pruning may be responsible for the tyloses observed in OPS plants. The greater lengths and higher frequencies of the rays in SSCS trees ay be due to the greater diaeters of their branches. ur results suggest that . glabra develops structural adaptations to the restinga micro-environmental variations during its development

Phenolic compounds from the rhizome of Renealmia nicolaioides Loes.: a new diarylheptanoid

Abstract: This study aims to identify phenolic compounds in dichloromethane and methanolic extracts of the rhizome of Renealmia nicolaioides collected in the North Region of Brazil. Two known diarylheptanoids, 1,7-bis(4-hydroxyphenyl)-(1E)-1-hepten-3-one (1), and 5R-1,7-bis(4-hydroxyphenyl)-1E-hepten-5-ol (2), and a new one (1R,2S,5S)-2-hydroxy-1,7(p-hydroxyphenyl)-centrolobine (3), as well as one flavonoid, 3-metoxi-quercetin (4) were isolated by chromatographic procedure and identified by spectroscopic techniques (1H and13C NMR, HRMS and CD). The acetyl derivative of 2 was used to confirm its structure. All four compounds are reported for the first time for this genus, and this is the first occurrence of compound 1 as a natural metabolite. The results reported here are unprecedented for the genus Renealmia

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 apoptosis

The 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