当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Semisynthesis and Biological Evaluation of Xanthone Amphiphilics as Selective, Highly Potent Antifungal Agents to Combat Fungal Resistance.

Semisynthesis and Biological Evaluation of Xanthone Amphiphilics as Selective, Highly Potent Antifungal Agents to Combat Fungal Resistance.

Abstract：

:New efficient antifungal agents are urgently needed to treat drug-resistant fungal infections. Here, we designed and synthesized a series of cationic xanthone amphiphilics as antifungal agents from natural α-mangostin to combat fungal resistance. The attachment of cationic residues on the xanthone scaffold of α-mangostin resulted in interesting antifungal agents with a novel mode of action. Two lead compounds (1 and 2) showed potent antifungal activity against a wide range of fungal pathogens, including drug-resistant Candida albicans, Aspergillus, and Fusarium strains and low cytotoxicity and hemolytic activity against mammalian cells. Both compounds can kill fungus rapidly by directly disrupting fungal cell membranes and avoid developing drug resistance. Additionally, compound 1 exhibited potent in vivo antifungal activity in the murine model of fungal keratitis. To our knowledge, membrane-targeting xanthone-based antifungals have not been reported previously. These results demonstrated that compounds 1 and 2 may be promising candidates for treating drug-resistant fungal infections.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Lin S,Sin WLW,Koh JJ,Lim F,Wang L,Cao D,Beuerman RW,Ren L,Liu S

doi

10.1021/acs.jmedchem.7b01348

subject

Has Abstract

pub_date

2017-12-28 00:00:00

pages

10135-10150

issue

24

eissn

0022-2623

issn

1520-4804

journal_volume

60

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 1).

    abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm040215+

    authors： Tremont SJ,Lee LF,Huang HC,Keller BT,Banerjee SC,Both SR,Carpenter AJ,Wang CC,Garland DJ,Huang W,Jones C,Koeller KJ,Kolodziej SA,Li J,Manning RE,Mahoney MW,Miller RE,Mischke DA,Rath NP,Fletcher T,Reinhard EJ,Tol

    更新日期：2005-09-08 00:00:00

  • Back door modulation of the farnesoid X receptor: design, synthesis, and biological evaluation of a series of side chain modified chenodeoxycholic acid derivatives.

    abstract：:Carbamate derivatives of bile acids were synthesized with the aim of systematically exploring the potential for farnesoid X receptor (FXR) modulation endowed with occupancy of the receptor's back door, localized between loops H1-H2 and H4-H5. Since it was previously shown that bile acids bind to FXR by projecting the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060294k

    authors： Pellicciari R,Gioiello A,Costantino G,Sadeghpour BM,Rizzo G,Meyer U,Parks DJ,Entrena-Guadix A,Fiorucci S

    更新日期：2006-07-13 00:00:00

  • Synthesis, biodistribution, and primate imaging of fluorine-18 labeled 2beta-carbo-1'-fluoro-2-propoxy-3beta-(4-chlorophenyl)tr opanes. Ligands for the imaging of dopamine transporters by positron emission tomography.

    abstract：:2beta-(R)-Carbo-1-fluoro-2-propoxy-3beta-(4-chlorophenyl) tro pane ((R)-FIPCT, R-6) and 2beta-(S)-carbo-1-fluoro-2-propoxy-3beta-(4-chlorophenyl) tro pane ((S)-FIPCT, S-6) were prepared and evaluated in vitro and in vivo for dopamine transporter (DAT) selectivity and specificity. High specific activity [(18)F](R)-FIPC...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9902234

    authors： Xing D,Chen P,Keil R,Kilts CD,Shi B,Camp VM,Malveaux G,Ely T,Owens MJ,Votaw J,Davis M,Hoffman JM,BaKay RA,Subramanian T,Watts RL,Goodman MM

    更新日期：2000-02-24 00:00:00

  • Comparative binding energy analysis considering multiple receptors: a step toward 3D-QSAR models for multiple targets.

    abstract：:Comparative binding energy analysis, a technique to derive receptor-based three-dimensional quantitative structure-activity relationships (3D-QSAR), is herein extended to consider both affinity and selectivity in the derivation of the QSAR model. The extension is based on allowing multiple structurally related recepto...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060350h

    authors： Murcia M,Morreale A,Ortiz AR

    更新日期：2006-10-19 00:00:00

  • Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitary cells.

    abstract：:Inhibition of growth hormone (GH) and prolactin (PRL) release from the anterior pituitary gland is mediated through somatostatin receptor subtypes sst2 and sst5. It has been found that somatostatin (SS) analogues that are selective for both receptor subtypes are more effective at inhibiting GH and PRL release than mon...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050376t

    authors： Moore SB,van der Hoek J,de Capua A,van Koetsveld PM,Hofland LJ,Lamberts SW,Goodman M

    更新日期：2005-10-20 00:00:00

  • Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.

    abstract：:The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activat...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060435i

    authors： Martin MW,Newcomb J,Nunes JJ,McGowan DC,Armistead DM,Boucher C,Buchanan JL,Buckner W,Chai L,Elbaum D,Epstein LF,Faust T,Flynn S,Gallant P,Gore A,Gu Y,Hsieh F,Huang X,Lee JH,Metz D,Middleton S,Mohn D,Morgenster

    更新日期：2006-08-10 00:00:00

  • CNS Physicochemical Property Space Shaped by a Diverse Set of Molecules with Experimentally Determined Exposure in the Mouse Brain.

    abstract：:Understanding the "limits and boundaries" of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward "traditional" aminergic targets and commonly describe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,收录出版

    doi：10.1021/acs.jmedchem.6b01469

    authors： Rankovic Z

    更新日期：2017-07-27 00:00:00

  • Discovery of Novel Small Molecule Dual Inhibitors Targeting Toll-Like Receptors 7 and 8.

    abstract：:Endosomal toll-like receptors (TLRs) 7 and 8 recognize viral single-stranded RNAs, a class of imidazoquinoline compounds, 8-oxo-adenosines, 8-aminobenzodiazepines, pyrimidines, and guanosine analogues. Substantial evidence is present linking chronic inflammation mediated specifically by TLR7 to the progression of auto...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01201

    authors： Padilla-Salinas R,Anderson R,Sakaniwa K,Zhang S,Nordeen P,Lu C,Shimizu T,Yin H

    更新日期：2019-11-27 00:00:00

  • Spirovesamicols: conformationally restricted analogs of 2-(4-phenylpiperidino)cyclohexanol (vesamicol, AH5183) as potential modulators of presynaptic cholinergic function.

    abstract：:In an effort to develop selective inhibitors of vesicular acetylcholine storage, we have synthesized a series of semirigid vesamicol receptor ligands based on the structure of 2-(4-phenylpiperidino)-cyclohexanol (vesamicol, AH5183, 1). In these compounds, the planes of the phenyl and piperidyl moieties of the parent l...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00042a010

    authors： Efange SM,Khare AB,Foulon C,Akella SK,Parsons SM

    更新日期：1994-08-05 00:00:00

  • Pharmacophore analysis of the nuclear oxysterol receptor LXRalpha.

    abstract：:A cell-free assay was developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment of a peptide from the steroid receptor coactivator 1 (SRC1) to the nuclear receptor. Using this ligand-sensing assay (LiSA), the structural requirements for activation of the receptor by oxysterols a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0004749

    authors： Spencer TA,Li D,Russel JS,Collins JL,Bledsoe RK,Consler TG,Moore LB,Galardi CM,McKee DD,Moore JT,Watson MA,Parks DJ,Lambert MH,Willson TM

    更新日期：2001-03-15 00:00:00

  • Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies.

    abstract：:Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm8000949

    authors： Wen X,Sun H,Liu J,Cheng K,Zhang P,Zhang L,Hao J,Zhang L,Ni P,Zographos SE,Leonidas DD,Alexacou KM,Gimisis T,Hayes JM,Oikonomakos NG

    更新日期：2008-06-26 00:00:00

  • Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins.

    abstract：:The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were test...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801153y

    authors： Samorì C,Guerrini A,Varchi G,Fontana G,Bombardelli E,Tinelli S,Beretta GL,Basili S,Moro S,Zunino F,Battaglia A

    更新日期：2009-02-26 00:00:00

  • Synthesis and broad-spectrum antiviral activity of 7,8-dihydro-7-methyl-8-thioxoguanosine.

    abstract：:2,6,8-Trichloro-7-methylpurine (3) was converted to 2-chloro-8,9-dihydro-7-methyl-8-thioxopurin-6(1H)-one (5) by utilizing the difference in reactivity of the 2-, 6-, and 8-positions in the trichloropurine ring system to nucleophilic displacement. Compound 5 was subsequently glycosylated with 1-O-acetyl-2,3,5-tri-O-be...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00170a013

    authors： Henry EM,Kini GD,Larson SB,Robins RK,Alaghamandan HA,Smee DF

    更新日期：1990-08-01 00:00:00

  • Discovery of the first nonpeptidic, small-molecule, highly selective somatostatin receptor subtype 5 antagonists: a chemogenomics approach.

    abstract：:We disclose the first selective, nonpeptidic, small-molecule somatostatin receptor subtype 5 (SST5R) antagonists that were identified by a chemogenomics approach based on the analysis of the homology of amino acids defining the putative consensus drug binding site of SST5R. With this strategy, opioid, histamine, dopam...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701143p

    authors： Martin RE,Green LG,Guba W,Kratochwil N,Christ A

    更新日期：2007-12-13 00:00:00

  • Potential antitumor agents. 39. Anilino ring geometry of amsacrine and derivatives: relationship to DNA binding and antitumor activity.

    abstract：:The clinical antileukemic drug amsacrine and analogues are thought to exert their biological activity by binding tightly but reversibly to DNA, with the acridine chromophore intercalated and the anilino group making additional binding contact in the minor groove of the double helix. In this binding model the steric en...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00365a014

    authors： Denny WA,Atwell GJ,Baguley BC

    更新日期：1983-11-01 00:00:00

  • Improved therapeutic efficacy of doxorubicin through conjugation with a novel peptide drug delivery technology (Vectocell).

    abstract：:Improvement in the therapeutic index of doxorubicin, a cytotoxic molecule, has been sought through its chemical conjugation to short (15-23 amino acid) peptide sequences called Vectocell peptides. Vectocell peptides are highly charged drug delivery peptides and display a number of characteristics that make them attrac...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0606591

    authors： Meyer-Losic F,Quinonero J,Dubois V,Alluis B,Dechambre M,Michel M,Cailler F,Fernandez AM,Trouet A,Kearsey J

    更新日期：2006-11-16 00:00:00

  • Structure-Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers.

    abstract：:Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01356

    authors： Siegrist R,Pozzi D,Jacob G,Torrisi C,Colas K,Braibant B,Mawet J,Pfeifer T,de Kanter R,Roch C,Kessler M,Moon R,Corminboeuf O,Bezençon O

    更新日期：2016-12-08 00:00:00

  • Synthesis and evaluation of novel radioligands for positron emission tomography imaging of metabotropic glutamate receptor subtype 1 (mGluR1) in rodent brain.

    abstract：:We designed three novel positron emission tomography ligands, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-4-[(11)C]methoxy-N-methylbenzamide ([(11)C]6), 4-[(18)F]fluoroethoxy-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]7), and 4-[(18)F]fluoropropoxy-N-[4-[6-(isopro...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201590g

    authors： Fujinaga M,Yamasaki T,Yui J,Hatori A,Xie L,Kawamura K,Asagawa C,Kumata K,Yoshida Y,Ogawa M,Nengaki N,Fukumura T,Zhang MR

    更新日期：2012-03-08 00:00:00

  • Isotope effects in enzymatic N-demethylation of tertiary amines.

    abstract：:The N-demethylation of 1-(N-methyl-N-trideuteriomethylamino)-3-phenylpropane (1) by rodent liver homogenates was studied. The ratio of 1-trideuteriomethylamino-3-phenylpropane (2)/1-methylamino-3-phenylpropane (3) was determined by gc-ms. The ratio of 2/3 in the product of N-demethylation of 1 by liver homogenate from...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00238a021

    authors： Abdel-Monem MM

    更新日期：1975-04-01 00:00:00

  • Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa-opioid receptor antagonist.

    abstract：:Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049172n

    authors： Chauvignac C,Miller CN,Srivastava SK,Lewis JW,Husbands SM,Traynor JR

    更新日期：2005-03-10 00:00:00

  • Discovery and structure-activity relationships of novel piperidine inhibitors of farnesyltransferase.

    abstract：:A novel piperidine series of farnesyltransferase (FTase) inhibitors is described. Systematic medicinal chemistry studies starting with the lead compound, discovered from a 5-nitropiperidin-2-one combinatorial library, resulted in a potent series of novel FTase inhibitors. We found that all of four substituents of the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020522k

    authors： Nara S,Tanaka R,Eishima J,Hara M,Takahashi Y,Otaki S,Foglesong RJ,Hughes PF,Turkington S,Kanda Y

    更新日期：2003-06-05 00:00:00

  • Beta-adrenergic blocking agents. 22. 1-Phenoxy-3-[[(substituted-amido) alkyl]amino]-2-propanols.

    abstract：:The synthesis of a series of 1-phenoxy-3-[[(substituted-amido)alkyl]amino]-2-propanols is described. Many of the compounds are more potent than propanolol as beta blockers, while having cardioselectivity comparable to that of practolol, when given intravenously to anesthetized cats. The structure-activity relationship...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00353a004

    authors： Lare MS,Smith LH

    更新日期：1982-11-01 00:00:00

  • Targeting the Allosteric Pathway That Interconnects the Core-Functional Scaffold and the Distal Phosphorylation Sites for Specific Dephosphorylation of Bcl-2.

    abstract：:Protein phosphorylation is the most significant post-translational modification for regulating cellular activities, but site-specific modulation of phosphorylation is still challenging. Using three-dimensional NMR spectra, molecular dynamics simulations, and alanine mutations, we identified that the interaction networ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01290

    authors： Wang Z,Song T,Guo Z,Cao K,Chen C,Feng Y,Wang H,Yin F,Zhou S,Dai J,Zhang Z

    更新日期：2020-11-25 00:00:00

  • Metal-dependent inhibition of HIV-1 integrase.

    abstract：:Human immunodeficiency virus type 1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Therefore, IN inhibitors are being sought for chemotherapy against AIDS. We had previously identified a series of salicylhydrazides as potent inhibitors of IN in vitro (Neamati, N.; et al. J. Med. Chem. 199...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0201417

    authors： Neamati N,Lin Z,Karki RG,Orr A,Cowansage K,Strumberg D,Pais GC,Voigt JH,Nicklaus MC,Winslow HE,Zhao H,Turpin JA,Yi J,Skalka AM,Burke TR Jr,Pommier Y

    更新日期：2002-12-19 00:00:00

  • Synthesis and evaluation of phosphorus containing, specific CDK9/CycT1 inhibitors.

    abstract：:Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401742r

    authors： Németh G,Greff Z,Sipos A,Varga Z,Székely R,Sebestyén M,Jászay Z,Béni S,Nemes Z,Pirat JL,Volle JN,Virieux D,Gyuris Á,Kelemenics K,Ay E,Minarovits J,Szathmary S,Kéri G,Orfi L

    更新日期：2014-05-22 00:00:00

  • Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and their activity against RNase H function of reverse transcriptase.

    abstract：:A series of antiviral basic quinolinonyl diketo acid derivatives were developed as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values below 100 nM for strand transfer and showed a 2 order of magnitude selectivity over 3'-processing. These strand transfer selective inhibitors also inhibited H...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm5001503

    authors： Costi R,Métifiot M,Chung S,Cuzzucoli Crucitti G,Maddali K,Pescatori L,Messore A,Madia VN,Pupo G,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Corona A,Pommier Y,Marchand C,Di San

    更新日期：2014-04-24 00:00:00

  • Structure-Activity Relationships and Characterization of Highly Selective, Long-Acting, Peptide-Based Cholecystokinin 1 Receptor Agonists.

    abstract：:A group of peptide-based, long-acting, stable, highly selective cholecystokinin 1 receptor (CCK-1R) agonists with the potential to treat obesity has been identified and characterized, based on systematic investigation of synthetic CCK-8 analogues with N-terminal linkage to fatty acids. Sulfated Tyr in such compounds w...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01558

    authors： Sensfuss U,Kruse T,Skyggebjerg RB,Uldam HK,Vestergaard B,Huus K,Vinther TN,Reinau ME,Schéele S,Clausen TR

    更新日期：2019-02-14 00:00:00

  • X-ray Structure Analysis of Indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) Bound to Human Serum Albumin Reveals Two Ruthenium Binding Sites and Provides Insights into the Drug Binding Mechanism.

    abstract：:Ruthenium(III) complexes are promising candidates for anticancer drugs, especially the clinically studied indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (NKP-1339). Several studies have emphasized the likely role of human ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00600

    authors： Bijelic A,Theiner S,Keppler BK,Rompel A

    更新日期：2016-06-23 00:00:00

  • Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan.

    abstract：:Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving ch...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01891

    authors： Naro Y,Ankenbruck N,Thomas M,Tivon Y,Connelly CM,Gardner L,Deiters A

    更新日期：2018-07-26 00:00:00

  • Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors.

    abstract：:A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3K...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00193

    authors： Thakur A,Tawa GJ,Henderson MJ,Danchik C,Liu S,Shah P,Wang AQ,Dunn G,Kabir M,Padilha EC,Xu X,Simeonov A,Kharbanda S,Stone R,Grewal G

    更新日期：2020-04-23 00:00:00