Bcl-2 proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, has been implicated in the progression and survival of multiple tumor types and become a validated and attractive target for cancer therapy. In this work, a series of 1-phenyl-1H-indole derivatives has been designed and synthesized. The preliminary biological studies (binding assay for Bcl-2 proteins and MTT assay) suggested that some active compounds showed potent inhibitory activities on Bcl-2/Mcl-1 without binding on Bcl-X Furthermore, Compound 9c and 9h showed better anti-proliferative activity than WL-276.
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http://dx.doi.org/10.1016/j.bmc.2017.08.024 | DOI Listing |
Bioorg Med Chem
October 2017
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China. Electronic address:
Bcl-2 proteins, such as B-cell lymphoma (Bcl-2) protein, myeloid cell leukemia sequence 1 (Mcl-1) protein, has been implicated in the progression and survival of multiple tumor types and become a validated and attractive target for cancer therapy. In this work, a series of 1-phenyl-1H-indole derivatives has been designed and synthesized. The preliminary biological studies (binding assay for Bcl-2 proteins and MTT assay) suggested that some active compounds showed potent inhibitory activities on Bcl-2/Mcl-1 without binding on Bcl-X Furthermore, Compound 9c and 9h showed better anti-proliferative activity than WL-276.
View Article and Find Full Text PDFInvest New Drugs
August 2016
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, L1, 17176, Stockholm, SE, Sweden.
We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show that RX871024, but not another insulinotropic imidazoline compound (BL11282), suppressed AMPK activity in MIN6 cells.
View Article and Find Full Text PDFChem Biol Drug Des
November 2015
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory against Metabolic Diseases, Guangzhou Higher Education Mega Centre, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Inhibition of p38 mitogen-activated protein kinases (MAPKs) would allow significant modulation of the neuroinflammation condition associated with Alzheimer's disease (AD). Inspired from the pharmacophore of natural NF-κB and p38α MAPK inhibitor 5,6-dehydrokawain and p38α MAPK inhibitors 1a, 1-pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl)ureas, and 1b, a class of indole-pyrimidinyl compounds which were patented respectively, we designed, de novo synthesized, and evaluated two kinds of novel series of lactone benzoyl hydrazine derivatives and 2-nitro-1-phenyl-1H-indole derivatives in an effort to develop pharmacologically tractable agents to alleviate the progression of AD. Fourteen of the seventeen synthesized compounds exhibit significant inhibitory effect on the nitric oxide (NO) production induced by lipopolysaccharide (LPS)-induced microglia activation with IC50 less than the control 5,6-dehydrokawain.
View Article and Find Full Text PDFActa Physiol (Oxf)
March 2009
Department of Clinical Science, Division of Endocrine Pharmacology, University of Lund, Malmö, Sweden.
Aim: The role of islet nitric oxide (NO) production in insulin-releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on beta-cell function might be related to perturbations of islet NO production.
Methods: Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment.
Am J Physiol Endocrinol Metab
January 2002
Endocrine and Diabetes Unit, Department of Molecular Medicine, Karolinska Institutet, S-171 76 Stockholm, Sweden.
The insulinotropic activity of the imidazoline derivative RX871024 was compared in pancreatic islets from nondiabetic Wistar rats and spontaneously diabetic Goto-Kakizaki (GK) rats. RX871024 significantly stimulated insulin secretion in islets from both animal groups. The insulinotropic activity of RX871024 was higher than that of the sulfonylurea glibenclamide.
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