The potential of P1 site alterations in peptidomimetic protease inhibitors as suggested by virtual screening and explored by the use of C-C-coupling reagents.

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：:Here we report the synthesis of a number of compounds structurally related to arginine methyltransferase inhibitor 1 (AMI-1). The structural alterations that we made included: 1) the substitution of the sulfonic groups with the bioisosteric carboxylic groups; 2) the replacement of the ureidic function with a bis-amidi...

journal_title：ChemMedChem

authors： Castellano S,Milite C,Ragno R,Simeoni S,Mai A,Limongelli V,Novellino E,Bauer I,Brosch G,Spannhoff A,Cheng D,Bedford MT,Sbardella G

更新日期：2010-03-01 00:00:00

abstract：:Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential thera...

journal_title：ChemMedChem

authors： Kessler D,Mayer M,Zahn SK,Zeeb M,Wöhrle S,Bergner A,Bruchhaus J,Ciftci T,Dahmann G,Dettling M,Döbel S,Fuchs JE,Geist L,Hela W,Kofink C,Kousek R,Moser F,Puchner T,Rumpel K,Scharnweber M,Werni P,Wolkerstorfer B,

更新日期：2020-12-04 00:00:00

abstract：:Using the original approach, a series of metallated N-confused porphyrins and metallated porphyrins have been synthesized and characterized. For all the synthesized porphyrins, in vitro studies of cytotoxic activity against K562, U937, HL-60, Jurkat, A549 and HeLa cancer cell lines, the ability to induce apoptosis and...

journal_title：ChemMedChem

authors： Halder N,Dzhemileva LU,Ramazanov IR,D'yakonov VA,Dzhemilev UM,Rath H

更新日期：2020-04-03 00:00:00

abstract：:The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recen...

journal_title：ChemMedChem

authors： Xiong XF,Poulsen MH,Hussein RA,Nørager NG,Strømgaard K

更新日期：2014-12-01 00:00:00

abstract：:Steroid derivatives bearing fluorescent groups such as anthracene, dansyl, deazaflavin, and pyrene attached to C6 were synthesized. These compounds are unique inhibitors of cytochrome P450 3A4 (CYP3A4) and display similar IC(50) values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipi...

journal_title：ChemMedChem

authors： Chougnet A,Grinkova Y,Ricard D,Sligar S,Woggon WD

更新日期：2007-05-01 00:00:00

abstract：:The present work describes some recent approaches to novel 3-oxabicyclo[3.2.0]heptane-type nucleosides structurally similar to the potent anti-HIV agent stavudine (d4T). To gain knowledge at the molecular level relevant for further synthetic designs, the lack of activity of these compounds was investigated by computat...

journal_title：ChemMedChem

authors： Figueras A,Miralles-Llumà R,Flores R,Rustullet A,Busqué F,Figueredo M,Font J,Alibés R,Maréchal JD

更新日期：2012-06-01 00:00:00

abstract：:Indolicidin (IR13), a 13-residue antimicrobial peptide from the cathelicidin family, is known to exhibit a broad spectrum of antimicrobial activity against various microorganisms. This peptide inhibits bacterial DNA synthesis resulting in cell filamentation. However, the precise mechanism remains unclear and requires ...

journal_title：ChemMedChem

authors： Ghosh A,Kar RK,Jana J,Saha A,Jana B,Krishnamoorthy J,Kumar D,Ghosh S,Chatterjee S,Bhunia A

更新日期：2014-09-01 00:00:00

abstract：:Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type ...

journal_title：ChemMedChem

authors： Al-Asri J,Gyémánt G,Fazekas E,Lehoczki G,Melzig MF,Wolber G,Mortier J

更新日期：2016-11-07 00:00:00

abstract：:Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and i...

journal_title：ChemMedChem

authors： Brullo C,Rapetti F,Alfei S,Maric I,Rizzelli F,Mapelli M,Rosano C,Viale M,Bruno O

更新日期：2020-06-04 00:00:00

abstract：:Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin ch...

journal_title：ChemMedChem

authors： Meirelles MA,Braga CB,Ornelas C,Pilli RA

更新日期：2019-08-06 00:00:00

abstract：:A strategy that combines virtual screening and structure-guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4-hydroxycoumarins, fenamic acids, and N-(alkylcarbonyl)anthranilic acids. Structure-guided selection of fragments targeting the inner subsite of the ...

journal_title：ChemMedChem

authors： Fritzson I,Svensson B,Al-Karadaghi S,Walse B,Wellmar U,Nilsson UJ,da Graça Thrige D,Jönsson S

更新日期：2010-04-06 00:00:00

abstract：:We previously described synapsin III (Syn III) as a synaptic phosphoprotein that controls dopamine release in cooperation with α-synuclein (aSyn). Moreover, we found that in Parkinson's disease (PD), Syn III also participates in aSyn aggregation and toxicity. Our recent observations point to threo-methylphenidate (MPH...

journal_title：ChemMedChem

authors： Casiraghi A,Longhena F,Straniero V,Faustini G,Newman AH,Bellucci A,Valoti E

更新日期：2020-07-20 00:00:00

abstract：:The concise synthesis and structure-activity relationship (SAR) studies of 3-aroylindoles were carried out in an effort to improve the potency and solubility of anticancer drug candidate BPR0L075 (8) by exploring structure modifications through three regimens: substitution of the B ring, at the N1 position, and of the...

journal_title：ChemMedChem

authors： Liou JP,Mahindroo N,Chang CW,Guo FM,Lee SW,Tan UK,Yeh TK,Kuo CC,Chang YW,Lu PH,Tung YS,Lin KT,Chang JY,Hsieh HP

更新日期：2006-10-01 00:00:00

abstract：:Having recently identified a so-far unexplored area adjacent to the known binding site of allosteric mitogen-activated protein kinase kinase (MEK) inhibitors, we now report an extension of these studies by combining our new side chains with different MEK inhibitor cores in a modular manner. Replacement of the amide he...

journal_title：ChemMedChem

authors： Hartung IV,Pühler F,Neuhaus R,Scholz A,Siemeister G,Geisler J,Hillig RC,von Ahsen O,Hitchcock M

更新日期：2015-12-01 00:00:00

abstract：:Abnormally high corticosteroid levels are responsible for the onset of serious hormone-related diseases, and the inhibition of their biosynthesis by targeting cytochrome P450 (CYP) isoforms CYP11B1 and CYP11B2 has emerged as a promising strategy to restore healthy physiological levels of corticosteroids. With the aim ...

journal_title：ChemMedChem

authors： Gobbi S,Hu Q,Zimmer C,Belluti F,Rampa A,Hartmann RW,Bisi A

更新日期：2016-08-19 00:00:00

abstract：:In an attempt to develop potent anticancer agents, a series of 2-anilinonicotinyl-linked acrylamide conjugates were designed, synthesized, and evaluated for cytotoxic activity against various human cancer cell lines, anti-tubulin activity and cell-cycle effects. Among the series, compounds 6 d [(E)-N-(6-fluorobenzo[d]...

journal_title：ChemMedChem

authors： Kamal A,Ashraf M,Khan MN,Nimbarte VD,Faazil S,Subba Reddy NV,Taj S

更新日期：2014-03-28 00:00:00

abstract：:The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily. This protein has a number of physiological functions, including protection of the human body from xenobiotics. The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in c...

journal_title：ChemMedChem

authors： Marighetti F,Steggemann K,Hanl M,Wiese M

更新日期：2013-01-01 00:00:00

abstract：:Because only a few studies have investigated the affinity and functional activity of NMDA receptor open channel blockers under the same assay conditions, a comparative study of common open channel blockers is of major interest. The pharmacological activities of MK-801, phencyclidine (PCP), dexoxadrol, etoxadrol, (S)- ...

journal_title：ChemMedChem

authors： Temme L,Schepmann D,Schreiber JA,Frehland B,Wünsch B

更新日期：2018-03-06 00:00:00

abstract：:A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. ...

journal_title：ChemMedChem

authors： Kamal A,Dastagiri D,Ramaiah MJ,Reddy JS,Bharathi EV,Srinivas C,Pushpavalli SN,Pal D,Pal-Bhadra M

更新日期：2010-11-08 00:00:00

abstract：:Drugs may have polypharmacological phenomena, that is, in addition to the desired target, they may also bind to many undesired or unknown physiological targets. As a result, they often exert side effects. In some cases, off-target interactions may lead to drug repositioning or to explaining a drug's mode of action. He...

journal_title：ChemMedChem

authors： Patel H,Lucas X,Bendik I,Günther S,Merfort I

更新日期：2015-07-01 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：:Cellular chaperones that belong to the heat-shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5...

journal_title：ChemMedChem

authors： Lillsunde KE,Tomašič T,Schult P,Lohmann V,Kikelj D,Tammela P

更新日期：2019-02-05 00:00:00

abstract：:Up to 45 % of deaths in developed nations can be attributed to chronic fibroproliferative diseases, highlighting the need for effective therapies. The RGD (Arg-Gly-Asp) integrin αvβ1 was recently investigated for its role in fibrotic disease, and thus warrants therapeutic targeting. Herein we describe the identificati...

journal_title：ChemMedChem

authors： Hatley RJD,Barrett TN,Slack RJ,Watson ME,Baillache DJ,Gruszka A,Washio Y,Rowedder JE,Pogány P,Pal S,Macdonald SJF

更新日期：2019-07-17 00:00:00

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：:The emergence and dissemination of multidrug resistant (MDR) pathogens resistant to nearly all available antibiotics poses a significant threat in clinical therapy. Among them, Klebsiella pneumoniae clinical isolates overexpressing KPC-2 carbapenemase are the most worrisome, extending bacterial resistance to last-reso...

journal_title：ChemMedChem

authors： Celenza G,Vicario M,Bellio P,Linciano P,Perilli M,Oliver A,Blazquez J,Cendron L,Tondi D

更新日期：2018-04-06 00:00:00

abstract：:Iridium(III) complexes of the type [Ir(η(5) -C5 Me5 )Cl2 {Ph2 PCH2 CH2 CH2 S(O)x Ph-κP}] (x=0-2; 1-3) and [Ir(η(5) -C5 Me5 )Cl{Ph2 PCH2 CH2 CH2 S(O)x Ph-κP,κS}][PF6 ] (x=0-1; 4 and 5) with 3-(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph2 PCH2 CH2 CH2 S(O)x Ph were designed, synthesized, a...

journal_title：ChemMedChem

authors： Ludwig G,Ranđelović I,Maksimović-Ivanić D,Mijatović S,Bulatović MZ,Miljković D,Korb M,Lang H,Steinborn D,Kaluđerović GN

更新日期：2014-07-01 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：:Iron is essential for the pathogenicity and virulence of Mycobacterium tuberculosis, which synthesises salicyl-capped siderophores (mycobactins) to acquire this element from the host. MbtA is the adenylating enzyme that catalyses the initial reaction of mycobactin biosynthesis and is solely expressed by mycobacteria. ...

journal_title：ChemMedChem

authors： Ferguson L,Wells G,Bhakta S,Johnson J,Guzman J,Parish T,Prentice RA,Brucoli F

更新日期：2019-10-04 00:00:00

abstract：:The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and t...

journal_title：ChemMedChem

authors： Erdélyi M,Navarro-Vázquez A,Pfeiffer B,Kuzniewski CN,Felser A,Widmer T,Gertsch J,Pera B,Díaz JF,Altmann KH,Carlomagno T

更新日期：2010-06-07 00:00:00