19013-10-6Relevant articles and documents
Design, synthesis and biological evaluation of novel EGFR/HER2 dual inhibitors bearing a oxazolo[4,5-g]quinazolin-2(1H)-one scaffold
Yin, Siyuan,Tang, Chunming,Wang, Bin,Zhang, Ying,Zhou, Liliang,Xue, Lingjing,Zhang, Can
, p. 26 - 36 (2016/05/24)
For the purpose of developing novel EGFR/HER2 tyrosine kinases inhibitors with high inhibition activity and low toxicity, two novel series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives as EGFR/HER2 dual inhibitors introducing two electrophiles 2-(2-bromoacetyl)ethyl and 2-(2-chloroacetoxy)ethyl group as side-chain at 1-position respectively and evaluated their EGFR and HER2 inhibition activity and toxicity comparing with Lapatinib. All these compounds were evaluated by EGFR and HER2 kinase inhibition and two anti-proliferation assays in vitro. Most of the designed compounds exhibited moderate to high inhibition activity against EGFR and HER2. Especially, compounds 11o, 11p, 12e and 12f presented high inhibition against EGFR and HER2. Furthermore, compounds 11p and 12f also had well exhibition to excellent anti-proliferation activity against human lung adenocarcinoma cell line (A549) and human breast cancer cell line (SK-Br3), and 12f also exhibited the lowest toxicity against human embryonic lung fibroblast cell line (HELF) cell. Finally, compound 12f presented remarkably higher inhibition efficacy towards tumour growth than Lapatinib in a mouse lewis lung cancer (LLC) xenograft model.
Investigation of supramolecular architectures of bent-shaped pyridine derivatives: From a three-ring crystalline compound towards five-ring mesogens
Tri?ovi?, Nemanja,Antanasijevi?, Jelena,Rogan, Jelena,Poleti, Dejan,Tóth-Katona, Tibor,Salamonczyk, Miroslaw,Jákli, Antal,Fodor-Csorba, Katalin
, p. 6977 - 6985 (2016/08/10)
In search of novel photoactive liquid crystals, we have synthesized a series of five-ring pyridine-based bent-core compounds bearing different substituents at the peripheral phenyl rings (CH3O, Cl and NO2). Their mesomorphic behaviour has been investigated by polarizing optical microscopy, differential scanning calorimetry and X-ray scattering, and then compared with the unsubstituted parent compound. The introduction of the methoxy groups at the peripheral phenyl rings of the bent core results in a non-mesomorphic compound, whereas the chloro- and nitro-substituted compounds form enantiotropic B1-like phases. Significant changes in the textures and transition temperatures of the mesophase have been observed under UV light. The present investigation of the mesomorphic properties of the synthesized compounds, coupled with the analysis of the molecular packing of the related three-ring compounds, will help design self-organized molecules suitable for UV indicators.
Development of hypoxia-inducible factor (HIF)-1α inhibitors: Effect of ortho-carborane substituents on HIF transcriptional activity under hypoxia
Nakamura, Hiroyuki,Yasui, Yuka,Maruyama, Minako,Minegishi, Hidemitsu,Ban, Hyun Seung,Sato, Shinichi
, p. 806 - 810 (2013/02/25)
A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI50) using the MTT assay. Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC50: 1.9 ± 0.4 and 1.4 ± 0.2 μM, respectively). Both compounds suppressed HIF-1α accumulation in a concentration-dependent manner. The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC50: 6.80 ± 0.25 μM) and this inhibition activity was higher than that of ETB (IC50: 10.9 ± 0.63 μM).