Tetracyclic indolines as a novel class of β-lactam-selective resistance-modifying agent for MRSA.


:Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relationships of a novel class of RMAs, tetracyclic indolines. These selectively potentiate β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) without antibacterial or β-lactamase inhibitory activity on their own. The most potent analogue, 6a, showed strong potentiation of amoxicillin/clavulanic acid in a variety of hospital-acquired and community-acquired MRSA strains with low mammalian toxicity. These compounds may be further developed to extend the clinic life span of β-lactam antibiotics.


Eur J Med Chem


Zhu Y,Cleaver L,Wang W,Podoll JD,Walls S,Jolly A,Wang X




Has Abstract


2017-01-05 00:00:00












  • Inhibition of vertebrate aldehyde oxidase as a therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis.

    abstract::The aldehyde oxidases (AOXs) are a small sub-family of cytosolic molybdo-flavoenzymes, which are structurally conserved proteins and broadly distributed from plants to animals. AOXs play multiple roles in both physiological and pathological processes and AOX inhibition is of increasing significance in the development ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Qiao Y,Maiti K,Sultana Z,Fu L,Smith R

    更新日期:2020-02-01 00:00:00

  • Optimization of 2-(3-(arylalkyl amino carbonyl) phenyl)-3-(2-methoxyphenyl)-4-thiazolidinone derivatives as potent antitumor growth and metastasis agents.

    abstract::A series of 2,3-diaryl-4-thiazolidinone derivatives were synthesized and evaluated for their antiproliferative properties against two well-known cancer cell lines (A549 as human lung cancer and MDA-MB-231 as human breast cancer). Structure activity relationship (SAR) analysis resulted in the discovery of 2-(3-(arylalk...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wu J,Yu L,Yang F,Li J,Wang P,Zhou W,Qin L,Li Y,Luo J,Yi Z,Liu M,Chen Y

    更新日期:2014-06-10 00:00:00

  • A novel bis-furan scaffold for transthyretin stabilization and amyloid inhibition.

    abstract::The design and synthesis of a novel bis-furan scaffold tailored for high efficiency at inhibiting transthyretin amyloid formation is reported. In vitro results show that the discovered compounds are more efficient inhibitors of amyloid formation than tafamidis, a drug currently used in the treatment of familial amyloi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Simões CJV,Almeida ZL,Costa D,Jesus CSH,Cardoso AL,Almeida MR,Saraiva MJ,Pinho E Melo TMVD,Brito RMM

    更新日期:2016-10-04 00:00:00

  • Synthesis of new 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1,3-thiazolino[5,4-b]quinoxaline derivatives and evaluation of their antiamoebic activity.

    abstract::In an effort to develop potent antiamoebic agents, we have synthesized chalcones (1-8), amino-5-substituted-(3-phenyl(2-pyrazolinyl))methane-1-thione derivatives (1a-8a) and 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1,3-thiazolino[5,4-b]quinoxaline derivatives (1b-8b) and evaluated for their in vitro antiamoebic activi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Budakoti A,Bhat AR,Azam A

    更新日期:2009-03-01 00:00:00

  • Design, synthesis and identification of silicon-containing HCV NS5A inhibitors with pan-genotype activity.

    abstract::Modification of a HCV NS5A inhibitor, ombitasvir, led to the identification of 10d with improved pan-genotype NS5A inhibition and better pharmacokinetic properties. The key structural changes to ombitasvir include bioisosteric replacement of carbon with silicon atom. Compared with ombitasvir, the activity of anti-HCV ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liu B,Gai K,Qin H,Liu X,Cao Y,Lu Q,Lu D,Chen D,Shen H,Song W,Zhang Y,Wang X,Xu H,Zhang Y

    更新日期:2018-03-25 00:00:00

  • Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3'-C-methyl-ribonucleosides as antitumor agents.

    abstract::A series of N6-aminopurine-9-β-D-ribonucleosides and ribose-modified 3'-C-methyl analogues substituted at N6-position with a small group like hydroxy, methoxy or amino group or at C2(N6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N6-Hydrazino-9-β-D-ribofuranos...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cappellacci L,Petrelli R,Franchetti P,Vita P,Kusumanchi P,Kumar M,Jayaram HN,Zhou B,Yen Y,Grifantini M

    更新日期:2011-05-01 00:00:00

  • LUMO energy of model compounds of bispyridinium compounds as an index for the inhibition of choline kinase.

    abstract::Eleven derivatives of 1,1'-[1,2-ethylenebis(benzene-1,4-diylmethylene)]bis(4-pyridinium) dibromides bearing various groups at C-4 of the pyridinium moiety were synthesized and examined for their inhibition of choline kinase (ChoK) and antiproliferative activities. The C-4 substituents include electron-releasing, neutr...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Campos J,del Carmen Núñez M,Rodríguez V,Entrena A,Hernández-Alcoceba R,Fernández F,Lacal JC,Gallo MA,Espinosa A

    更新日期:2001-03-01 00:00:00

  • Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates.

    abstract::The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymp...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ibáñez E,Plano D,Font M,Calvo A,Prior C,Palop JA,Sanmartín C

    更新日期:2011-01-01 00:00:00

  • Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4'-fluorophenyl)-imidazo[2,1-b][1,3,4]thiadiazole derivatives as potent anticancer agents.

    abstract::Levamisole, the imidazo[2,1-b]thiazole derivative has been reported as a potential antitumor agent. In the present study, we synthesized, characterized and evaluated biological activity of its novel analogues with substitution in the aralkyl group and on imidazothiadiazole molecules with same chemical backbone but dif...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Karki SS,Panjamurthy K,Kumar S,Nambiar M,Ramareddy SA,Chiruvella KK,Raghavan SC

    更新日期:2011-06-01 00:00:00

  • Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co-transporter 2 inhibitors.

    abstract::Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are the current focus on the indication for the management of hyperglycemia in diabetes. Here, a novel series of C-linked indolylxyloside-based inhibitors of SGLT2 has been discovered. Structure-activity relationship studies revealed that substituents at the...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yao CH,Song JS,Chen CT,Yeh TK,Hsieh TC,Wu SH,Huang CY,Huang YL,Wang MH,Liu YW,Tsai CH,Kumar CR,Lee JC

    更新日期:2012-09-01 00:00:00

  • Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA.

    abstract::Various substituted 3-aryl-1-isoquinolinamines were designed and synthesized based on the previously constructed CoMFA model. Most of the synthesized compounds showed excellent potency in eight different human tumor cell lines as expected. In order to find the exact cytotoxic mechanism of these 3-aryl-1-isoquinolinami...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yang SH,Van HT,Le TN,Khadka DB,Cho SH,Lee KT,Lee ES,Lee YB,Ahn CH,Cho WJ

    更新日期:2010-11-01 00:00:00

  • Present status of quinoxaline motifs: excellent pathfinders in therapeutic medicine.

    abstract::Quinoxalines belong to a class of excellent heterocyclic scaffolds owing to their wide biological properties and diverse therapeutic applications in medicinal research. They are complementary in shapes and charges to numerous biomolecules they interact with, thereby resulting in increased binding affinity. The pharmac...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Ajani OO

    更新日期:2014-10-06 00:00:00

  • 4-Phenyl quinoline derivatives as potential serotonin receptor ligands with antiproliferative activity.

    abstract::Antagonists of signaling receptors are often effective non-toxic therapeutic agents. Over the years, there have been evidences describing the role of serotonin or 5-hydroxytryptamine (5-HT) in development of cancer. Although there are reports on the antiproliferative effects of some serotonin receptor antagonists, the...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Joshi PV,Sayed AA,RaviKumar A,Puranik VG,Zinjarde SS

    更新日期:2017-08-18 00:00:00

  • Synthesis and pharmacological investigation of novel 4-(2-methylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H(1)-antihistaminic agents.

    abstract::A series of novel 1-substituted-4-(2-methylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones were synthesized by the cyclization of 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one with various one carbon donors. The starting material 2-hydrazino-3-(2-methylphenyl)-3H-quinazolin-4-one was synthesized from 2-methyl ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Alagarsamy V,Rupeshkumar M,Kavitha K,Meena S,Shankar D,Siddiqui AA,Rajesh R

    更新日期:2008-11-01 00:00:00

  • Synthesis and antimycobacterial activity of new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives.

    abstract::As a continuation of our research and with the aim of obtaining new anti-tuberculosis agents which can improve the current chemotherapeutic anti-tuberculosis treatments, forty-three new quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and evaluated for in vitro anti-tuberculosis activity against M...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Moreno E,Ancizu S,Pérez-Silanes S,Torres E,Aldana I,Monge A

    更新日期:2010-10-01 00:00:00

  • Synthesis and anticancer activity of new dihydropyrimidinone derivatives.

    abstract::A series of dihydropyrimidinone derivatives bearing various N-heterocyclic moieties was designed and synthesized. Twelve new compounds were screened for their cytotoxic activity using 60 cancer cell lines according to NCI (USA) protocol. Compound 19 showed a significant activity against NCI-H460, SK-MEL-5, and HL-60 (...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mostafa AS,Selim KB

    更新日期:2018-08-05 00:00:00

  • Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents.

    abstract::Twenty-five novel pyranochalcone derivatives were synthesized and evaluated for their in vitro and in vivo antiproliferative activities. Among them, compound 10i exhibited superior potent activity against 21 tumor cell lines including multidrug resistant phenotype with the IC50 values ranged from 0.09 to 1.30 μM. In a...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cao D,Han X,Wang G,Yang Z,Peng F,Ma L,Zhang R,Ye H,Tang M,Wu W,Lei K,Wen J,Chen J,Qiu J,Liang X,Ran Y,Sang Y,Xiang M,Peng A,Chen L

    更新日期:2013-04-01 00:00:00

  • Recent insights into synthetic β-carbolines with anti-cancer activities.

    abstract::Cancer, an uncontrolled and rapid proliferation of abnormal cells, has become one of the leading cause of death worldwide. The development of resistance among the numerous drugs in clinical use has provided strong impetus for the identification and development of novel cancer therapeutics. β-carbolines constitute an i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Kumar S,Singh A,Kumar K,Kumar V

    更新日期:2017-12-15 00:00:00

  • Design, synthesis, in-vitro, in-vivo and in-silico studies of pyrrolidine-2,5-dione derivatives as multitarget anti-inflammatory agents.

    abstract::In recent years, drug discovery paradigm has been shifted from conventional single target inhibition toward multitarget design concept. In current research, we have reported synthesis, in-vitro, in-vivo and acute toxicity determination of N-substituted pyrrolidine-2,5-dione derivatives as multitarget anti-inflammatory...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jan MS,Ahmad S,Hussain F,Ahmad A,Mahmood F,Rashid U,Abid OU,Ullah F,Ayaz M,Sadiq A

    更新日期:2020-01-15 00:00:00

  • Design, synthesis and biological evaluation of novel pyridine-thiazolidinone derivatives as anticancer agents: Targeting human carbonic anhydrase IX.

    abstract::In order to obtain novel Human carbonic anhydrase IX (CAIX) inhibitors, a series of pyridine-thiazolidinone derivatives was synthesized and characterized by various spectroscopic techniques. The binding affinity of the compounds was measured by fluorescence binding studies and enzyme inhibition activity using esterase...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ansari MF,Idrees D,Hassan MI,Ahmad K,Avecilla F,Azam A

    更新日期:2018-01-20 00:00:00

  • Identification of putative steroid-binding sites in human ABCB1 and ABCG2.

    abstract::Homology modelling was used to generate three-dimensional structures of the nucleotide-binding domains (NBDs) of human ABCB1 and ABCG2. Interactions between a series of steroidal ligands and transporter NBDs were investigated using an in silico docking approach. C-terminal ABCB1 NBD (ABCB1 NBD2) was predicted to bind ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mares-Sámano S,Badhan R,Penny J

    更新日期:2009-09-01 00:00:00

  • Synthesis of new chiral 2,5-disubstituted 1,3,4-thiadiazoles possessing gamma-butenolide moiety and preliminary evaluation of in vitro anticancer activity.

    abstract::A new series of chiral 1,3,4-thiadiazoles derivatives possessing gamma-substituted butenolide moiety were synthesized and evaluated for in vitro anticancer properties. All the compounds showed good anticancer activities against Hela cell lines. Of all the studied compounds, compound 9e exhibited the best inhibitory ac...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Wei MX,Feng L,Li XQ,Zhou XZ,Shao ZH

    更新日期:2009-08-01 00:00:00

  • Synthesis and evaluation of antimicrobial activity of 4H-pyrimido[2,1-b]benzothiazole, pyrazole and benzylidene derivatives of curcumin.

    abstract::A novel, one-pot, simple, efficient procedure for 4H-pyrimido[2,1-b]benzothiazole (4a-h), pyrazole (6a-d) and benzylidene (7a-d) derivatives of curcumin under solvent and solvent free conditions in microwave with good yield is have been synthesized. The synthesized compounds were evaluated for their antibacterial acti...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sahu PK,Sahu PK,Gupta SK,Thavaselvam D,Agarwal DD

    更新日期:2012-08-01 00:00:00

  • Design and discovery of 4-anilinoquinazoline-urea derivatives as dual TK inhibitors of EGFR and VEGFR-2.

    abstract::EGFR and VEGFR-2 are involved in pathological disorders and the progression of different kinds of tumors, the combined blockade of EGFR and VEGFR signaling pathways appears to be an attractive approach to cancer therapy. In this work, a series of 4-anilinoquinazoline derivatives containing substituted diaryl urea or g...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang HQ,Gong FH,Ye JQ,Zhang C,Yue XH,Li CG,Xu YG,Sun LP

    更新日期:2017-01-05 00:00:00

  • Pharmacophore-based virtual screening and Bayesian model for the identification of potential human leukotriene A4 hydrolase inhibitors.

    abstract::Leukotriene A4 hydrolase (LTA4H), an enzyme involved in the conversion of LTA4 to LTB4, is an emerging and important anti-inflammatory target. This study demonstrates the development of quantitative pharmacophore hypothesis and Bayesian model and their applications in identification of potential human LTA4H (hLTA4H) i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Thangapandian S,John S,Sakkiah S,Lee KW

    更新日期:2011-05-01 00:00:00

  • Structural and biological studies of mononuclear palladium(II) complexes containing N-substituted thiosemicarbazones.

    abstract::New complexes of Pd(II) with N-substituted thiosemicarbazone (1)-(3) have been synthesised and characterised by elemental analyses, IR, electronic, (1)H NMR spectroscopies. The electrochemical behaviour of the complexes has been tested by using cyclic voltammetry. The crystal structures of the complexes have been dete...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Prabhakaran R,Renukadevi SV,Karvembu R,Huang R,Mautz J,Huttner G,Subashkumar R,Natarajan K

    更新日期:2008-02-01 00:00:00

  • Discovery of small molecular (D)-leucinamides as potent, Notch-sparing γ-secretase modulators.

    abstract::Structural optimization of the prior lead 3 led to the small molecular (D)-leucinamides with potent modulating activity and Notch-sparing selectivity on the proteolytic processing of amyloid-β precursor proteins. The N-(R)-epoxypropyl analog 10c exhibited potent γ-secretase modulation compared to DAPT and showed subst...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liao YF,Tang YC,Chang MY,Wang BJ,Hu MK

    更新日期:2014-05-22 00:00:00

  • New 5-substituted thiazolo[3,2-b][1,2,4]triazol-6-ones: synthesis and anticancer evaluation.

    abstract::Following [2+3]-cyclocondensation reaction of 1,2,4-triazole-3(5)-thiol with N-arylmaleimides or with monochloroacetic acid and oxocompounds, N-(R-phenyl)-(6-oxo-5,6-dihydro[1,3]thiazol[3,2-b][1,2,4]triazol-5-yl)acetamides (1-5) and 5-ylidene-[1,3]thiazolo[3,2-b][1,2,4]triazol-6-ones (6-11) were synthesized as possibl...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lesyk R,Vladzimirska O,Holota S,Zaprutko L,Gzella A

    更新日期:2007-05-01 00:00:00

  • New groups of antimycobacterial agents: 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 6-chloro-3-phenyl-2H-1,3-benzoxazine-2,4(3H)-dithiones.

    abstract::A series of 6-chloro-3-phenyl-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones 3 and a series of 6-chloro-3-phenyl-2H-1,3-benzoxazine-2, 4(3H)-dithiones 4 were synthesized by melting 6-chloro-3-phenyl-2H-1, 3-benzoxazine-2,4(3H)-dione and its derivatives substituted on the phenyl ring 2 with tetraphosphorus decasulfide. Compoun...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Waisser K,Gregor J,Kubicová L,Klimesová V,Kunes J,Machácek M,Kaustová J

    更新日期:2000-07-01 00:00:00

  • Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay.

    abstract::In the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rohe A,Göllner C,Wichapong K,Erdmann F,Al-Mazaideh GM,Sippl W,Schmidt M

    更新日期:2013-03-01 00:00:00