Histone deacetylase inhibitors with enhanced enzymatic inhibition effects and potent in vitro and in vivo antitumor activities.

abstract：:A series of new substituted 7-phenyl-3H-pyrrolo[3,2-f]quinolin-9-ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI(50) values in the nanomolar range. The active com...

journal_title：ChemMedChem

authors： Ferlin MG,Bortolozzi R,Brun P,Castagliuolo I,Hamel E,Basso G,Viola G

更新日期：2010-08-02 00:00:00

abstract：:Histone deacetylases (HDACs) are promising drug targets for a variety of therapeutic applications. Herein we describe the design, synthesis, biological evaluation in cellular models of cancer, and preliminary drug metabolism and pharmacokinetic studies (DMPK) of a series of secondary and tertiary N-substituted 7-amino...

journal_title：ChemMedChem

authors： Abdelkarim H,Neelarapu R,Madriaga A,Vaidya AS,Kastrati I,Karumudi B,Wang YT,Taha TY,Thatcher GRJ,Frasor J,Petukhov PA

更新日期：2017-12-19 00:00:00

abstract：:Over the past few years, the number of people diagnosed with type 2 diabetes has increased owing to an unhealthy diet, a limited amount of exercise, and obesity. The search for novel and efficient antidiabetes agents has become an urgent task for scientists. Among the antidiabetes drugs, α-glucosidase inhibitor drugs ...

journal_title：ChemMedChem

authors： Liu Z,Ma S

更新日期：2017-06-07 00:00:00

abstract：:Nitrogen mustards are an important class of bifunctional alkylating agents routinely used in chemotherapy. They react with DNA as electrophiles through the formation of highly reactive aziridinium ion intermediates. The antibiotic 593A, with potential antitumor activity, can be considered a naturally occurring piperid...

journal_title：ChemMedChem

authors： Zuravka I,Roesmann R,Sosic A,Wende W,Pingoud A,Gatto B,Göttlich R

更新日期：2014-09-01 00:00:00

abstract：:A diverse group of proteins, the activities of which are precisely orchestrated during mitosis, have emerged as targets for cancer therapeutics; these include the Aurora kinases (AKs), Polo-like kinases (PLKs), and the kinesin spindle protein (KSP). KSP is essential for the proper separation of spindle poles during mi...

journal_title：ChemMedChem

authors： Song H,Zhou S,Wang R,Li S

更新日期：2013-11-01 00:00:00

abstract：:Half-sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7-trithiacyclononane [9]aneS(3) represent a promising class of apoptosis-inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the...

journal_title：ChemMedChem

authors： Bieda R,Dobroschke M,Triller A,Ott I,Spehr M,Gust R,Prokop A,Sheldrick WS

更新日期：2010-07-05 00:00:00

abstract：:The NLRP3 inflammasome is an important regulator of the sterile inflammatory response, and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL-1β)/IL-18, and pyroptotic cell death. Inappropriate activation ...

journal_title：ChemMedChem

authors： Baldwin AG,Tapia VS,Swanton T,White CS,Beswick JA,Brough D,Freeman S

更新日期：2018-02-20 00:00:00

abstract：:A class of compounds with a common thiazolo[3,2-a]pyrimidinone motif has been developed as general inhibitors of Bcl-2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization-based competitive binding assay. Its binding to the Bcl...

journal_title：ChemMedChem

authors： Zhou B,Li X,Li Y,Xu Y,Zhang Z,Zhou M,Zhang X,Liu Z,Zhou J,Cao C,Yu B,Wang R

更新日期：2011-05-02 00:00:00

abstract：:This paper describes the synthesis, characterisation, and cytotoxicity of a novel trinuclear platinum complex code named TH1. In addition to its activity against human ovarian cancer cell lines: A2780, A2780(cisR), and A2780(ZD0473R), cell uptake, DNA-binding, and the nature of the compound interaction with pBR322 pla...

journal_title：ChemMedChem

authors： Tayyem H,Huq F,Yu JQ,Beale P,Fisher K

更新日期：2008-01-01 00:00:00

abstract：:Cancer cells express high levels of CK2, and its inhibition leads to apoptosis. CK2 has therefore emerged as a new drug target for cancer therapy. A biligand inhibitor ARC-772 was constructed by conjugating 4-(2-amino-1,3-thiazol-5-yl)benzoic acid and a carboxylate-rich peptoid. ARC-772 was found to bind CK2 with a Kd...

journal_title：ChemMedChem

authors： Rahnel H,Viht K,Lavogina D,Mazina O,Haljasorg T,Enkvist E,Uri A

更新日期：2017-10-20 00:00:00

abstract：:The natural product piperlonguminine (PL) has been shown to exert potential anticancer activity against several types of cancer via elevation of reactive oxidative species (ROS). However, the application of PL has been limited due to its poor water solubility and moderate activity. To improve PL's potency, we designed...

journal_title：ChemMedChem

authors： Wang X,Qian J,Zhu P,Hua R,Liu J,Hang J,Meng C,Shan W,Miao J,Ling Y

更新日期：2020-10-21 00:00:00

abstract：:The ferrocenyl diphenol complexes 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (1) and 1,2-bis(4'-hydroxyphenyl)-1-ferrocenyl-but-1-ene [(Z)-2], which differ by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells (1 is far more cytotox...

journal_title：ChemMedChem

authors： Tonolo F,Salmain M,Scalcon V,Top S,Pigeon P,Folda A,Caron B,McGlinchey MJ,Toillon RA,Bindoli A,Jaouen G,Vessières A,Rigobello MP

更新日期：2019-10-04 00:00:00

abstract：:Polo-like kinase 1 (PLK1) plays crucial functions in multiple stages of mitosis and is considered to be a potential drug target for cancer therapy. The functions of PLK1 are mediated by its N-terminal kinase domain and C-terminal polo-box domain (PBD). Most inhibitors targeting the kinase domain of PLK1 have a selecti...

journal_title：ChemMedChem

authors： Shan HM,Shi Y,Quan J

更新日期：2015-01-01 00:00:00

abstract：:A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 μm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin-2(3H)...

journal_title：ChemMedChem

authors： Woodland A,Thompson S,Cleghorn LA,Norcross N,De Rycker M,Grimaldi R,Hallyburton I,Rao B,Norval S,Stojanovski L,Brun R,Kaiser M,Frearson JA,Gray DW,Wyatt PG,Read KD,Gilbert IH

更新日期：2015-11-01 00:00:00

abstract：:A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S. pneumoniae): ∼2-4 μg mL(-1) ; 2.55-5.09 μm] and cytotoxic [IC50 values (HeLa, KB, MCF-7, A549, HepG2 cells): ∼1.35-3.70 μm] ...

journal_title：ChemMedChem

authors： Domagalska J,Janas A,Pyta K,Pecyna P,Ruszkowski P,Celewicz L,Gajecka M,Bartl F,Przybylski P

更新日期：2016-09-06 00:00:00

abstract：:Singling out the truth: A combined application of STD-NMR, molecular docking, and CORCEMA-ST calculations is described as an attractive, easily applicable tool for the identification and validation of the binding site for allosteric ligands, with potential application as an aid in drug discovery research. ...

journal_title：ChemMedChem

authors： Zhang W,Li R,Shin R,Wang Y,Padmalayam I,Zhai L,Krishna NR

更新日期：2013-10-01 00:00:00

abstract：:The role of beta-aminovinyl ketones as synthetic intermediates has been well categorised, but recent developments have shown an interesting array of applications and new chemotherapeutic potential, both in the preparation of biologically active heterocycles and as pharmacophores in their own right.Medicinal chemists a...

journal_title：ChemMedChem

authors： Gaber HM,Bagley MC

更新日期：2009-07-01 00:00:00

abstract：:We recently reported a vitamin B(12) (B(12)) based insulin conjugate that produced significantly decreased blood glucose levels in diabetic STZ-rat models. The results of this study posed a fundamental question, namely what implications does B(12) conjugation have on insulin's interaction with the insulin receptor (IR...

journal_title：ChemMedChem

authors： Petrus AK,Allis DG,Smith RP,Fairchild TJ,Doyle RP

更新日期：2009-03-01 00:00:00

abstract：:Based on the crystal structures of human alpha-GalCer-CD1d and iNKT-alpha-GalCer-CD1d complexes, nonglycosidic analogues of alpha-GalCer were synthesized. They activate iNKT cells resulting in dendritic cell maturation and the priming of antigen-specific T and B cells. Therefore, they are attractive adjuvants in vacci...

journal_title：ChemMedChem

authors： Reddy BG,Silk JD,Salio M,Balamurugan R,Shepherd D,Ritter G,Cerundolo V,Schmidt RR

更新日期：2009-02-01 00:00:00

abstract：:Structural preorganization to fix bioactive conformations at protein binding sites is a popular strategy to enhance binding affinity during late-stage optimization. The rationale for this enhancement relates to entropic advantages assigned to rigidified versus flexible ligands. We analyzed a narrow series of peptidomi...

journal_title：ChemMedChem

authors： Rühmann EH,Rupp M,Betz M,Heine A,Klebe G

更新日期：2016-02-04 00:00:00

abstract：:The synthesis of a novel group of quinacridine-based ligands (MMQs) is described along with an evaluation of their G-quadruplex binding properties. A set of biophysical assays was applied to characterize their interaction with DNA quadruplexes: FRET-melting experiments and equilibrium microdialysis were used to evalua...

journal_title：ChemMedChem

authors： Hounsou C,Guittat L,Monchaud D,Jourdan M,Saettel N,Mergny JL,Teulade-Fichou MP

更新日期：2007-05-01 00:00:00

abstract：:The serotonin transporter (SERT) is one of the neurotransmitter transporters that plays a critical role in the regulation of endogenous amine concentrations and therefore is an important target for therapeutic agents affecting the central nervous system. The recently published, high resolution X-ray structure of the c...

journal_title：ChemMedChem

authors： Jørgensen AM,Tagmose L,Jørgensen AM,Topiol S,Sabio M,Gundertofte K,Bøgesø KP,Peters GH

更新日期：2007-06-01 00:00:00

abstract：:Given its role in the mediation of energy and glucose homeostasis, the G-protein-coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand...

journal_title：ChemMedChem

authors： Zhu J,Ye Y,Ning M,Mándi A,Feng Y,Zou Q,Kurtán T,Leng Y,Shen J

更新日期：2013-07-01 00:00:00

abstract：:Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required...

journal_title：ChemMedChem

authors： Dichiara M,Marrazzo A,Prezzavento O,Collina S,Rescifina A,Amata E

更新日期：2017-08-22 00:00:00

abstract：:Despite significant advances made in the last decade in the understanding of molecular mechanisms of sepsis and in the development of clinically relevant therapies, sepsis remains the leading cause of mortality in intensive care units with increasing incidence worldwide. Toll-like receptor 4 (TLR4)-a transmembrane pat...

journal_title：ChemMedChem

authors： Borio A,Holgado A,Garate JA,Beyaert R,Heine H,Zamyatina A

更新日期：2018-11-06 00:00:00

abstract：:The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Here, we present the efficient synthesis of five Glc-GlcA-Glc sequenced and one Glc-IdoA-Glc sequenced non-glycosaminoglycan, heparin-related trisaccharides with various...

journal_title：ChemMedChem

authors： Lisztes E,Mező E,Demeter F,Horváth L,Bősze S,Tóth BI,Borbás A,Herczeg M

更新日期：2021-01-12 00:00:00

abstract：:Efavirenz (EFV), an antiretroviral that interacts clinically with co-administered drugs via activation of the pregnane X receptor (PXR), is extensively metabolized by the cytochromes P450. We tested whether its primary metabolite, 8-hydroxyEFV (8-OHEFV) can activate PXR and potentially contribute to PXR-mediated drug-...

journal_title：ChemMedChem

authors： Narayanan B,Lade JM,Heck CJS,Dietz KD,Wade H,Bumpus NN

更新日期：2018-04-06 00:00:00

abstract：:P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-...

journal_title：ChemMedChem

authors： Liu B,Qiu Q,Zhao T,Jiao L,Li Y,Huang W,Qian H

更新日期：2015-02-01 00:00:00

abstract：:The renin angiotensin aldosterone system (RAAS) is a hormonal cascade involved in the regulation of blood pressure and electrolyte balance, and represents a common target for the treatment of various diseases including hypertension, heart failure, and diabetes. Herein we present a novel 18 F-labeled derivative of the ...

journal_title：ChemMedChem

authors： Hoffmann M,Chen X,Hirano M,Arimitsu K,Kimura H,Higuchi T,Decker M

更新日期：2018-12-06 00:00:00

abstract：:A library of 40,000 compounds was screened for inhibitors of 2-methylerythritol 2,4-cyclodiphosphate synthase (IspF) protein from Arabidopsis thaliana using a photometric assay. A thiazolopyrimidine derivative resulting from the high-throughput screen was found to inhibit the IspF proteins of Mycobacterium tuberculosi...

journal_title：ChemMedChem

authors： Geist JG,Lauw S,Illarionova V,Illarionov B,Fischer M,Gräwert T,Rohdich F,Eisenreich W,Kaiser J,Groll M,Scheurer C,Wittlin S,Alonso-Gómez JL,Schweizer WB,Bacher A,Diederich F

更新日期：2010-07-05 00:00:00