A Novel Hybrid of Chloroquine and Primaquine Linked by Gold(I): Multitarget and Multiphase Antiplasmodial Agent.

abstract：:A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 ...

journal_title：ChemMedChem

authors： Angapelly S,Sri Ramya PV,Angeli A,Supuran CT,Arifuddin M

更新日期：2017-10-09 00:00:00

abstract：:Targeting the biosynthetic pathway of neuroactive steroids with specific 18 kDa translocator protein (TSPO) ligands may be a viable therapeutic approach for a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between binding affinity and in vitro steroidogenic efficacy has li...

journal_title：ChemMedChem

authors： Costa B,Taliani S,Da Pozzo E,Barresi E,Robello M,Cavallini C,Cosconati S,Da Settimo F,Novellino E,Martini C

更新日期：2017-08-22 00:00:00

abstract：:A set of piperonylic acid derived hydrazones with variable isatin moieties was synthesized and evaluated for their inhibitory activity against the enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidases A and B (MAO-A/B). The results of in vitro studies revealed IC50 values in the mic...

journal_title：ChemMedChem

authors： Vishnu MS,Pavankumar V,Kumar S,Raja AS

更新日期：2019-07-17 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：: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：:Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology. Potent, selective, brain-penetrant inhibitors of Plk-2 were obtained from a structure-guided drug discovery approach...

journal_title：ChemMedChem

authors： Aubele DL,Hom RK,Adler M,Galemmo RA Jr,Bowers S,Truong AP,Pan H,Beroza P,Neitz RJ,Yao N,Lin M,Tonn G,Zhang H,Bova MP,Ren Z,Tam D,Ruslim L,Baker J,Diep L,Fitzgerald K,Hoffman J,Motter R,Fauss D,Tanaka P,Dap

更新日期：2013-08-01 00:00:00

abstract：:We designed and synthesized two novel series of azapodophyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moie...

journal_title：ChemMedChem

authors： Labruère R,Gautier B,Testud M,Seguin J,Lenoir C,Desbène-Finck S,Helissey P,Garbay C,Chabot GG,Vidal M,Giorgi-Renault S

更新日期：2010-12-03 00:00:00

abstract：:Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone-dependent. Steroidal and non-steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the ...

journal_title：ChemMedChem

authors： Möller C,Bone W,Cleve A,Klar U,Rotgeri A,Rottmann A,Schultze-Mosgau MH,Wagenfeld A,Schwede W

更新日期：2018-11-06 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：: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：:Computer-guided drug design is a powerful tool for drug discovery. Herein we disclose the use of this approach for the discovery of dual FMS-like receptor tyrosine kinase-3 (FLT3)-Aurora A inhibitors against cancer. An Aurora hit compound was selected as a starting point, from which 288 virtual molecules were screened...

journal_title：ChemMedChem

authors： Chang Hsu Y,Ke YY,Shiao HY,Lee CC,Lin WH,Chen CH,Yen KJ,Hsu JT,Chang C,Hsieh HP

更新日期：2014-05-01 00:00:00

abstract：:The development and progression of chronic complications in diabetic patients, such as retinopathy, nephropathy, neuropathy, cataracts, and stroke, are related to the activation and/or overexpression of aldose reductase (ALR2), which is a member of the aldo-keto reductase superfamily. A structure-activity relationship...

journal_title：ChemMedChem

authors： Zhang S,Chen X,Parveen S,Hussain S,Yang Y,Jing C,Zhu C

更新日期：2013-04-01 00:00:00

abstract：:The gold standard for the treatment of metastatic colorectal cancer consists of combination chemotherapy. Over time, however, the development of chemoresistant tumor clones leads to relapse. It may be possible to overcome oxaliplatin chemoresistance in colorectal cancer cells by exploiting a complex obtained from the ...

journal_title：ChemMedChem

authors： Gandin V,Marzano C,Pelosi G,Ravera M,Gabano E,Osella D

更新日期：2014-06-01 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：:Digital Drug Discovery: Guest Editors Andreas Bender (University of Cambridge) and Nathan Brown (BenevolentAI) present the 20 articles included in this Special Issue on Cheminformatics in Drug Design. As they summarize each article, they also discuss the common themes within in silico drug discovery that these papers ...

journal_title：ChemMedChem

authors： Bender A,Brown N

更新日期：2018-03-20 00:00:00

abstract：:Octa-O-bis-(R,R)-Tartarate Ditellurane (SAS) is a new Te(IV) compound, comprised of two tellurium atoms, each liganded by four oxygen atoms from two carboxylates and two alkoxides of two tartaric acids. Unlike many other Te(IV) compounds, SAS was highly stable in aqueous solution. It interacted with thiols to form an ...

journal_title：ChemMedChem

authors： Yosef S,Brodsky M,Sredni B,Albeck A,Albeck M

更新日期：2007-11-01 00:00:00

abstract：:There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62,000 compound library a...

journal_title：ChemMedChem

authors： Spinks D,Shanks EJ,Cleghorn LA,McElroy S,Jones D,James D,Fairlamb AH,Frearson JA,Wyatt PG,Gilbert IH

更新日期：2009-12-01 00:00:00

abstract：:The disruption of aberrant protein-protein interactions (PPIs) with synthetic agents remains a challenging goal in contemporary medicinal chemistry but some progress has been made. One such dysregulated PPI is that between the anti-apoptotic Bcl-2 proteins, including myeloid cell leukemia-1 (Mcl-1), and the α-helical ...

journal_title：ChemMedChem

authors： Drennen B,Scheenstra JA,Yap JL,Chen L,Lanning ME,Roth BM,Wilder PT,Fletcher S

更新日期：2016-04-19 00:00:00

abstract：:Meridional rhodium(III) polypyridyl complexes of the type mer-[RhX(3)(DMSO)(pp)] (X=Cl, pp=phen 1, dpq 2, dppz 3; X=Br, pp=phen 4) represent a promising class of potent cytostatic agents for the treatment of lymphoma and leukemia. Exposure of their DMSO solutions to light leads to slow isomerization to mixtures of the...

journal_title：ChemMedChem

authors： Dobroschke M,Geldmacher Y,Ott I,Harlos M,Kater L,Wagner L,Gust R,Sheldrick WS,Prokop A

更新日期：2009-02-01 00:00:00

abstract：:Loperamide (1a), an opioid receptor agonist, is in clinical use as an antidiarrheal agent. Carbon/silicon exchange (sila-substitution) at the 4-position of the piperidine ring of 1a (R3 COH→R3 SiOH) leads to sila-loperamide (1b). Sila-loperamide was synthesized in a multistep procedure, starting from triethoxyvinylsil...

journal_title：ChemMedChem

authors： Geyer M,Wellner E,Jurva U,Saloman S,Armstrong D,Tacke R

更新日期：2015-05-01 00:00:00

abstract：:The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX-2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovasc...

journal_title：ChemMedChem

authors： Schuller HM,Kabalka G,Smith G,Mereddy A,Akula M,Cekanova M

更新日期：2006-06-01 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：:First reported in the late 1930s and partly explained in 1970, the antibacterial activity of pectin remained almost ignored until the late 1990s. The concomitant emergence of research on natural antibacterials and new usages of pectin polysaccharides, including those in medicine widely researched in Russia, has led to...

journal_title：ChemMedChem

authors： Ciriminna R,Fidalgo A,Meneguzzo F,Presentato A,Scurria A,Nuzzo D,Alduina R,Ilharco LM,Pagliaro M

更新日期：2020-08-28 00:00:00

abstract：:Oxoisoaporphine alkaloids are a family of oxoisoquinoline-derived alkaloids that were first isolated from the rhizome of Menispermum dauricum DC. (Menispermaceae). It has been demonstrated that oxoisoaporphine alkaloids possess various biological properties, such as cholinesterase and β-amyloid inhibition, acting as a...

journal_title：ChemMedChem

authors： Zhang J,Chen L,Sun J

更新日期：2018-07-06 00:00:00

abstract：:Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1beta and TNFalpha. Inhibition of p38 MAPK results in decreased expression of these cytokines. T...

journal_title：ChemMedChem

authors： Ziegler K,Hauser DR,Unger A,Albrecht W,Laufer SA

更新日期：2009-11-01 00:00:00

abstract：:Designed multitarget ligands are a popular approach to generating efficient and safe drugs, and fragment-based strategies have been postulated as a versatile avenue to discover multitarget ligand leads. To systematically probe the potential of fragment-based multiple ligand discovery, we have employed a large fragment...

journal_title：ChemMedChem

authors： Brunst S,Kramer JS,Kilu W,Heering J,Pollinger J,Hiesinger K,George S,Steinhilber D,Merk D,Proschak E

更新日期：2020-12-06 00:00:00

abstract：:The synthesis of SCF3 as well as SeCF3 isosteres of two OCF3 -containing drugs was achieved through visible light and copper-catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical and ADME properties without introducing intrinsic liabilities. The SCF3 and SeCF3 groups are more lipoph...

journal_title：ChemMedChem

authors： Ghiazza C,Billard T,Dickson C,Tlili A,Gampe CM

更新日期：2019-09-04 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：:From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and n...

journal_title：ChemMedChem

authors： Park SJ,Baars H,Mersmann S,Buschmann H,Baron JM,Amann PM,Czaja K,Hollert H,Bluhm K,Redelstein R,Bolm C

更新日期：2013-02-01 00:00:00

abstract：:Antimicrobial peptides (AMPs) are promising candidates to help circumvent antibiotic resistance, which is an increasing clinical problem. Amino-terminal copper and nickel (ATCUN) binding motifs are known to actively form reactive oxygen species (ROS) upon metal binding. The combination of these two peptidic constructs...

journal_title：ChemMedChem

authors： Libardo MD,Cervantes JL,Salazar JC,Angeles-Boza AM

更新日期：2014-08-01 00:00:00