当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and biological activity of anticancer ether lipids that are specifically released by phospholipase A2 in tumor tissue.

Synthesis and biological activity of anticancer ether lipids that are specifically released by phospholipase A2 in tumor tissue.

Abstract：

:The clinical use of anticancer lipids is severely limited by their ability to cause lysis of red blood cells prohibiting intravenous injection. Novel delivery systems are therefore required in order to develop anticancer ether lipids (AELs) into clinically useful anticancer drugs. In a recent article (J. Med. Chem. 2004, 47, 1694) we showed that it is possible to construct liposome systems composed of masked AELs that are activated by secretory phospholipase A2 in cancerous tissue. We present here the synthesis of six AELs and evaluate the biological activity of these bioactive lipids. The synthesized AEL 1-6 were tested against three different cancer cell lines. It was found that the stereochemistry of the glycerol headgroup in AEL-2 and 3 has a dramatic effect on the cytotoxicity of the lipids. AEL 1-4 were furthermore evaluated for their ability to prevent phosphorylation of the apoptosis regulating kinase Akt, and a correlation was found between their cytotoxic activity and their ability to inhibit Akt phosphorylation.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Andresen TL,Jensen SS,Madsen R,Jørgensen K

doi

10.1021/jm049006f

keywords:

subject

Has Abstract

pub_date

2005-11-17 00:00:00

pages

7305-14

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

48

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Inhibitors of Bacillus subtilis DNA polymerase III. 6-Anilinouracils and 6-(alkylamino)uracils.

    abstract：:Substituted 6-anilinouracils were found to be potent inhibitors of the replication-specific enzyme, DNA polymerase III, from Bacillus subtilis. Inhibition potency was maximized by inclusion of small alkyl groups or halogens in the meta and para positions of the phenyl ring; polar substituents decreased activity consi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00175a007

    authors： Wright GE,Brown NC

    更新日期：1980-01-01 00:00:00

  • New 5-unsubstituted dihydropyridines with improved CaV1.3 selectivity as potential neuroprotective agents against ischemic injury.

    abstract：:C5-unsubstituted-C6-aryl-1,4-dihydropyridines were prepared by a CAN-catalyzed multicomponent reaction from chalcones, β-dicarbonyl compounds, and ammonium acetate. These compounds were able to block Ca(2+) entry after a depolarizing stimulus and showed an improved Cav1.3/Cav1.2 selectivity in comparison with nifedipi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500263v

    authors： Tenti G,Parada E,León R,Egea J,Martínez-Revelles S,Briones AM,Sridharan V,López MG,Ramos MT,Menéndez JC

    更新日期：2014-05-22 00:00:00

  • Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations.

    abstract：:The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.8b00180

    authors： Young RJ,Leeson PD

    更新日期：2018-08-09 00:00:00

  • Synthesis and biological evaluation of the methyl esters of (+)-12-fluoro-13,14-dihydroprostaglandin F2alpha and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha.

    abstract：:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly signific...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00139a014

    authors： Grieco PA,Takigawa T

    更新日期：1981-07-01 00:00:00

  • Structure-activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor an

    abstract：:The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneou...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9005912

    authors： Singh J,Zeller W,Zhou N,Hategan G,Mishra RK,Polozov A,Yu P,Onua E,Zhang J,Ramírez JL,Sigthorsson G,Thorsteinnsdottir M,Kiselyov AS,Zembower DE,Andrésson T,Gurney ME

    更新日期：2010-01-14 00:00:00

  • Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.

    abstract：:A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1),...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970836l

    authors： Asano N,Nishida M,Kato A,Kizu H,Matsui K,Shimada Y,Itoh T,Baba M,Watson AA,Nash RJ,Lilley PM,Watkin DJ,Fleet GW

    更新日期：1998-07-02 00:00:00

  • Synthesis, antifertility activity, and protein binding affinity of 7(8 leads to 11 alpha)abeo steroids.

    abstract：:A series of 7(8 leads to 11 alpha)abeo steroids was synthesized by a modification of the previously described total synthesis of this class of compounds and evaluated for biological activity. In general, there was a marked reduction in the relative binding affinities of these compounds for the rabbit uterus estrogen a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00214a017

    authors： Wani MC,Rector DH,White DH,Pitt CG,Kimmel GL

    更新日期：1977-04-01 00:00:00

  • Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic.

    abstract：:We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm300631e

    authors： Savechenkov PY,Zhang X,Chiara DC,Stewart DS,Ge R,Zhou X,Raines DE,Cohen JB,Forman SA,Miller KW,Bruzik KS

    更新日期：2012-07-26 00:00:00

  • Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity.

    abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00685

    authors： Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

    更新日期：2016-10-13 00:00:00

  • Regulating bioactivity of Cu2+ bis-1,10-phenanthroline artificial metallonucleases with sterically functionalized pendant carboxylates.

    abstract：:The synthetic chemical nuclease, [Cu(1,10-phenanthroline)2](2+), has stimulated research within metallonuclease development and in the area of cytotoxic metallodrug design. Our analysis reveals, however, that this agent is "promiscuous" as it binds both dsDNA and protein biomolecules, without specificity, and induces ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401465m

    authors： Prisecaru A,McKee V,Howe O,Rochford G,McCann M,Colleran J,Pour M,Barron N,Gathergood N,Kellett A

    更新日期：2013-11-14 00:00:00

  • Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine.

    abstract：:A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00161a010

    authors： Cignarella G,Barlocco D,Pinna GA,Loriga M,Tofanetti O,Germini M,Sala F

    更新日期：1986-11-01 00:00:00

  • An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives.

    abstract：:On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenocepto...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00380a001

    authors： Macchia B,Balsamo A,Lapucci A,Martinelli A,Macchia F,Breschi MC,Fantoni B,Martinotti E

    更新日期：1985-02-01 00:00:00

  • Sterols as anticancer agents: synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis.

    abstract：:The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cel...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1007769

    authors： Carvalho JF,Silva MM,Moreira JN,Simões S,Sá e Melo ML

    更新日期：2010-11-11 00:00:00

  • Potential antisecretory antidiarrheals. 2. Alpha 2-adrenergic 2-[(aryloxy)alkyl]imidazolines.

    abstract：:Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00164a024

    authors： Moormann AE,Pitzele BS,Jones PH,Gullikson GW,Albin D,Yu SS,Bianchi RG,Sanguinetti EL,Rubin B,Grebner M

    更新日期：1990-02-01 00:00:00

  • Use of simple docking methods to screen a virtual library for heteroactivators of cytochrome P450 2C9.

    abstract：:Several laboratories have demonstrated that activation of drug metabolism by P450s may occur via a mechanism that resembles allosterism from an enzyme kinetic standpoint. Because the effector drug binding site may be located in the same P450 binding pocket where the drug substrate is located, the ability to find and c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060706p

    authors： Locuson CW,Gannett PM,Ayscue R,Tracy TS

    更新日期：2007-03-22 00:00:00

  • Further studies on the metabolism of carbidopa, (minus)-L-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate, in the human, Rhesus monkey, dog, and rat.

    abstract：:Major urinary metabolites of carbidopa have been identified. Estimates were made based on the recovery or radio activity or by glc analysis of pooled urine of the amounts of the urinary metabolites II (2-methyl-3'-methoxy-4'-hydroxyphenylpropionic acid), III (2-methyl-3,4-dihydroxyphenylpropionic acid), IV (3,4-dihydr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00236a004

    authors： Vickers S,Stuart EK,Hucker HB

    更新日期：1975-02-01 00:00:00

  • Nonpeptide somatostatin agonists with sst4 selectivity: synthesis and structure-activity relationships of thioureas.

    abstract：:Utilizing NNC 26-9100 (11) as a structural lead, a variety of nonpeptide derivatives of somatostatin were synthesized and evaluated for sst2 and sst4 receptor binding affinity. A novel thiourea scaffold was utilized to attach (1) a heteroaromatic nucleus to mimic the Trp8 residue, (2) a nonheteroaromatic nucleus to mi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980118e

    authors： Liu S,Tang C,Ho B,Ankersen M,Stidsen CE,Crider AM

    更新日期：1998-11-19 00:00:00

  • Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease.

    abstract：:Eleven new 12-amino-6,7,10,11-tetrahydro-7, 11-methanocycloocta[b]quinoline derivatives [tacrine (THA)-huperzine A hybrids, rac-21-31] have been synthesized as racemic mixtures and tested as acetylcholinesterase (AChE) inhibitors. For derivatives unsubstituted at the benzene ring, the highest activity was obtained for...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980620z

    authors： Camps P,El Achab R,Görbig DM,Morral J,Muñoz-Torrero D,Badia A,Eladi Baños J,Vivas NM,Barril X,Orozco M,Luque FJ

    更新日期：1999-08-26 00:00:00

  • Small Antimicrobial Agents Based on Acylated Reduced Amide Scaffold.

    abstract：:Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resista...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00640

    authors： Teng P,Huo D,Nimmagadda A,Wu J,She F,Su M,Lin X,Yan J,Cao A,Xi C,Hu Y,Cai J

    更新日期：2016-09-08 00:00:00

  • Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors.

    abstract：:Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential antitumor agents, but the most advanced inhibitor series reported to date are not orally bioavailable. A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm3012933

    authors： Lainchbury M,Matthews TP,McHardy T,Boxall KJ,Walton MI,Eve PD,Hayes A,Valenti MR,de Haven Brandon AK,Box G,Aherne GW,Reader JC,Raynaud FI,Eccles SA,Garrett MD,Collins I

    更新日期：2012-11-26 00:00:00

  • Structure-activity relationship of the ficin hydrolysis of phenyl hippurates. Comparison with papain, actinidin, and bromelain.

    abstract：:A study of the hydrolysis of 30 substituted-phenyl hippurates by the enzyme ficin has been made. From the results the following quantitative structure--activity relationship (QSAR) has been derived: log 1/Km = 0.79 pi'3 + 0.58 sigma + 0.28 MR4,5 + 3.70. In this expression Km is the Michaelis constant, pi'3 refers to t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00377a009

    authors： Carotti A,Casini G,Hansch C

    更新日期：1984-11-01 00:00:00

  • Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity.

    abstract：:A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000951n

    authors： van Acker FA,Hageman JA,Haenen GR,van Der Vijgh WJ,Bast A,Menge WM

    更新日期：2000-10-05 00:00:00

  • Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins.

    abstract：:A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00010

    authors： D de Araujo A,Lim J,Wu KC,Xiang Y,Good AC,Skerlj R,Fairlie DP

    更新日期：2018-04-12 00:00:00

  • Thiazolothiazepine inhibitors of HIV-1 integrase.

    abstract：:A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purifie...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990047z

    authors： Neamati N,Turpin JA,Winslow HE,Christensen JL,Williamson K,Orr A,Rice WG,Pommier Y,Garofalo A,Brizzi A,Campiani G,Fiorini I,Nacci V

    更新日期：1999-08-26 00:00:00

  • 4-N-, 4-S-, and 4-O-chloroquine analogues: influence of side chain length and quinolyl nitrogen pKa on activity vs chloroquine resistant malaria.

    abstract：:Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701478a

    authors： Natarajan JK,Alumasa JN,Yearick K,Ekoue-Kovi KA,Casabianca LB,de Dios AC,Wolf C,Roepe PD

    更新日期：2008-06-26 00:00:00

  • Design and Biological Evaluation of m-Xylene Thioether-Stapled Short Helical Peptides Targeting the HIV-1 gp41 Hexameric Coiled-Coil Fusion Complex.

    abstract：:Short peptide-based inhibition of fusion remains an attractive goal in antihuman immunodeficiency virus (HIV) research based on its potential for the development of technically and economically desirable antiviral agents. Herein, we report the use of the dithiol bisalkylation reaction to generate a series of m-xylene ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00882

    authors： Meng G,Pu J,Li Y,Han A,Tian Y,Xu W,Zhang T,Li X,Lu L,Wang C,Jiang S,Liu K

    更新日期：2019-10-10 00:00:00

  • Intensely potent doxorubicin analogues: structure-activity relationship.

    abstract：:N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorub...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9706980

    authors： Farquhar D,Cherif A,Bakina E,Nelson JA

    更新日期：1998-03-12 00:00:00

  • Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae.

    abstract：:Sterol 14α-demethylases (CYP51) are cytochrome P450 enzymes essential for sterol biosynthesis in eukaryotes and therapeutic targets for antifungal azoles. Multiple attempts to repurpose antifungals for treatment of human infections with protozoa (Trypanosomatidae) have been undertaken, yet so far none of them have rev...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01671

    authors： Friggeri L,Hargrove TY,Rachakonda G,Blobaum AL,Fisher P,de Oliveira GM,da Silva CF,Soeiro MNC,Nes WD,Lindsley CW,Villalta F,Guengerich FP,Lepesheva GI

    更新日期：2018-12-13 00:00:00

  • Pyrrolobenzodiazepine Dimer Antibody-Drug Conjugates: Synthesis and Evaluation of Noncleavable Drug-Linkers.

    abstract：:Three rationally designed pyrrolobenzodiazepine (PBD) drug-linkers have been synthesized via intermediate 19 for use in antibody-drug conjugates (ADCs). They lack a cleavable trigger in the linker and consist of a maleimide for cysteine antibody conjugation, a hydrophilic spacer, and either an alkyne (6), triazole (7)...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00736

    authors： Gregson SJ,Masterson LA,Wei B,Pillow TH,Spencer SD,Kang GD,Yu SF,Raab H,Lau J,Li G,Lewis Phillips GD,Gunzner-Toste J,Safina BS,Ohri R,Darwish M,Kozak KR,Dela Cruz-Chuh J,Polson A,Flygare JA,Howard PW

    更新日期：2017-12-14 00:00:00

  • Design, synthesis, and structure-activity relationships of benzophenone-based tetraamides as novel antibacterial agents.

    abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900519b

    authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

    更新日期：2009-08-27 00:00:00