Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.


:A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound 6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation.


Eur J Med Chem


More UA,Joshi SD,Aminabhavi TM,Kulkarni VH,Badiger AM,Lherbet C




Has Abstract


2015-04-13 00:00:00












  • New dimeric cyclodiphosph(V)azane complexes of Cr(III), Co(II), Ni(II), Cu(II), and Zn(II): preparation, characterization and biological activity studies.

    abstract::The complexes of type [CrLCl](2).3.5H(2)O and [ML(H(2)O)](2).nH(2)O in which M = Co(II); n = 1, Ni(II); n = 4, Cu(II); n = 0.5 and Zn(II); n = 2 ions and L is 1,3-dimethyl-2,4-dioxo-2',4'-bis(2iminothiophene)cyclodiphosph(V)azane, were prepared and their structures characterized by elemental analysis, IR, (1)H NMR, (3...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Alaghaz AN,Ammar RA

    更新日期:2010-04-01 00:00:00

  • Synthesis, biological evaluation, and molecular docking study of 3-(3'-heteroatom substituted-2'-hydroxy-1'-propyloxy) xanthone analogues as novel topoisomerase IIα catalytic inhibitor.

    abstract::Epoxide ring-opened xanthone derivatives were synthesized and tested for their topoisomerase inhibitory activity and cytotoxicity. Most of the compounds showed topo IIα specific inhibitory activity. To clarify the mechanism of action of these compounds, the most potent compound (compound 14) of the synthesized analogu...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jun KY,Lee EY,Jung MJ,Lee OH,Lee ES,Park Choo HY,Na Y,Kwon Y

    更新日期:2011-06-01 00:00:00

  • A glutathione-responsive photosensitizer with fluorescence resonance energy transfer characteristics for imaging-guided targeting photodynamic therapy.

    abstract::Here, we have synthesized and characterized a novel activatable photosensitizer (PS) 8a in which two well-designed boron dipyrromethene (BODIPY) derivatives are utilized as the photosensitizing fluorophore and quencher respectively, which are connected by a disulfide linker via two successive Cu (І) catalyzed click re...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cao JJ,Zhang MS,Li XQ,Yang DC,Xu G,Liu JY

    更新日期:2020-05-01 00:00:00

  • One pot synthesis of thiazolodihydropyrimidinones and evaluation of their anticancer activity.

    abstract::2-(5-Arylfurfurylidene/5-nitrofurfurylidene)-5-aryl-7-(2,4-dichloro-5-fluorophenyl)-5H-thiazolo[2,3-b]-pyrimidin-2(1H)-ones 5 and 6 are synthesized by a novel three component reaction of 4,6-diarylpyrimidino-2(1H)-thiones 4, monochloroacetic acid, arylfurfuraldehydes and 5-nitro-2-furfuraldenediacetate, respectively. ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Holla BS,Rao BS,Sarojini BK,Akberali PM

    更新日期:2004-09-01 00:00:00

  • Pharmacophore model for pentamidine analogs active against Plasmodium falciparum.

    abstract::Pentamidine and its analogs constitute a class of compounds that are known to be active against Plasmodium falciparum, which causes the most dangerous malarial infection. Malaria is a widespread disease known to affect hundreds of millions of people and presents a perceivable threat of spreading. Hence, there is a nee...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Athri P,Wenzler T,Tidwell R,Bakunova SM,Wilson WD

    更新日期:2010-12-01 00:00:00

  • Synthesis, biological evaluation and molecular docking studies of some pyrimidine derivatives.

    abstract::Some novel pyrimidine-5-carbonitrile derivatives bearing various substituent have been synthesized. The structures of target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their cytotoxic potency against certain human tum...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Fargualy AM,Habib NS,Ismail KA,Hassan AM,Sarg MT

    更新日期:2013-08-01 00:00:00

  • Stereoselective synthesis of (RP)-8-substituted-N⁶-acylated and N⁶-alkylated adenosine-3',5'-cyclic phosphorothioic acids as cAMP antagonists.

    abstract::N(6)-Monoalkylated, N(6)-dialkylated and N(6)-acylated (R(P))-adenosine 3',5'-cyclic phosphorothioic acids have been prepared by stereoselective syntheses from cAMP for a study of protein kinase A antagonist activity. The antagonist activity of the parent primary 6-amino cAMP derivative was reduced after N-monoalkylat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Andrei M,Bakkebø T,Klaveness J,Taskén K,Undheim K

    更新日期:2011-12-01 00:00:00

  • Discovery of a new selective inhibitor of A Disintegrin And Metalloprotease 10 (ADAM-10) able to reduce the shedding of NKG2D ligands in Hodgkin's lymphoma cell models.

    abstract::Hodgkin's lymphoma (HL) is the most common malignant lymphoma in young adults in the western world. This disease is characterized by an overexpression of ADAM-10 with increased release of NKG2D ligands, involved in an impaired immune response against tumor cells. We designed and synthesized two new ADAM-10 selective i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Camodeca C,Nuti E,Tepshi L,Boero S,Tuccinardi T,Stura EA,Poggi A,Zocchi MR,Rossello A

    更新日期:2016-03-23 00:00:00

  • Naphthalimide-based macrophage nucleus imaging probes.

    abstract::The photophysical properties of naphthalimide-based fluorophores can be easily tuned by chemical manipulation of the substituents on that privileged scaffold. Replacement of a OMe group at position 6 in 2-(hydroxyl)ethyl-naphthalimide derivatives by diverse amines, including 2-(hydroxyl)ethylamine, trans-(4-acetamido)...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Fueyo-González F,Fernández-Gutiérrez M,García-Puentes D,Orte A,González-Vera JA,Herranz R

    更新日期:2020-08-15 00:00:00

  • Synthesis, characterization and in vitro biological activity studies of Cu-M (M = Cu2+, Co2+, Ni2+, Mn2+, Zn2+) bimetallic complexes.

    abstract::Six new bimetallic complexes of the type CuCu, CuCo, CuNi, CuZn and CuMn were prepared. The structures of these complexes and the ligand have been proposed on the basis of FAB mass, elemental analysis, UV-vis, IR, EPR and CV studies. All the complexes completely cleave pBS (SK-) DNA at a concentration of 10 microM; ho...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rupesh KR,Deepalatha S,Krishnaveni M,Venkatesan R,Jayachandran S

    更新日期:2006-12-01 00:00:00

  • Anti-proliferative evaluation of monoterpene derivatives against leukemia.

    abstract::The cure rate of pediatric acute lymphoblastic leukemia (ALL) has significantly improved in the past thirty years, however not all patient cohorts respond well to current chemotherapy regimens. Among the high risk patient cohort is infants with MLL-rearranged (MLL-r) B-ALL, which remains dismal with an overall surviva...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gautam LN,Ling T,Lang W,Rivas F

    更新日期:2016-05-04 00:00:00

  • Synthesis, characterization and in vitro antibacterial activity of new steroidal 5-en-3-oxazolo and thiazoloquinoxaline.

    abstract::Steriodal heterocyclic systems namely cholest-5-en-3-oxazolo and thiazoloquinoxaline have been synthesized via the reaction of cholest-5-en-3-one semicarbazone/thiosemicarbazone with 2,3-dichloroquinoxaline at 80 degrees C in high yield. Cholest-5-en-3-one semicarbazone is obtained by the condensation of cholest-5-en-...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Khan SA

    更新日期:2008-09-01 00:00:00

  • Synthesis, spectroscopic and biological properties of bis(3-arylimidazolidinyl-1)methanes. A novel family of antimicrobial agents.

    abstract::Synthesis, spectroscopic and biological properties of new bis(3-arylimidazolidinyl-1)methanes are described. These compounds were synthesized by condensation reaction between N-arylethylenediamines and formaldehyde. Chemical structures were confirmed by means of their (1)H- and (13)C-NMR and mass spectroscopic data. I...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Perillo I,Repetto E,Caterina MC,Massa R,Gutkind G,Salerno A

    更新日期:2005-08-01 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

  • 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

  • 3,5-Diaryl-1H-pyrazolo[3,4-b]pyridines as potent tubulin polymerization inhibitors: Rational design, synthesis and biological evaluation.

    abstract::A series of novel 3,5-diaryl-1H-pyrazolo[3,4-b]pyridines as tubulin polymerization inhibitors targeting the colchicine site were designed via ring tethering strategy, which was supported by conformational analysis. The general, chemically unstable and rotational linker, carbanyl group, was locked by 1H-pyrazolo[3,4-b]...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zhai M,Liu S,Gao M,Wang L,Sun J,Du J,Guan Q,Bao K,Zuo D,Wu Y,Zhang W

    更新日期:2019-04-15 00:00:00

  • Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.

    abstract::A novel series of non-peptide proteasome inhibitors bearing the 1, 4-naphthoquinone scaffold and boronic acid warhead was developed. In the biological evaluation on the chymotrypsin-like activity of human 20S proteasome, five compounds showed IC50 values in the nanomolar range. Docking experiments into the yeast 20S p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ge Y,Li A,Wu J,Feng H,Wang L,Liu H,Xu Y,Xu Q,Zhao L,Li Y

    更新日期:2017-03-10 00:00:00

  • Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives.

    abstract::Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sources, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rodríguez-Hernández D,Barbosa LCA,Demuner AJ,Nain-Perez A,Ferreira SR,Fujiwara RT,de Almeida RM,Heller L,Csuk R

    更新日期:2017-11-10 00:00:00

  • 3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors.

    abstract::During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Carta A,Briguglio I,Piras S,Boatto G,La Colla P,Loddo R,Tolomeo M,Grimaudo S,Di Cristina A,Pipitone RM,Laurini E,Paneni MS,Posocco P,Fermeglia M,Pricl S

    更新日期:2011-09-01 00:00:00

  • Design, synthesis and bioactivities of TAR RNA targeting beta-carboline derivatives based on Tat-TAR interaction.

    abstract::A series of new beta-carboline derivatives 3-14 bearing guanidinium group or amino group-terminated side chain targeting the TAR RNA were designed and synthesized. Molecular modeling studies indicated that the minimal interaction energy was obtained for compound 11, which contained the optimal linker of three methylen...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yu X,Lin W,Pang R,Yang M

    更新日期:2005-09-01 00:00:00

  • Structure-activity relationship studies of lipophilic teicoplanin pseudoaglycon derivatives as new anti-influenza virus agents.

    abstract::Six series of semisynthetic lipophilic glycopeptide antibiotic derivatives were evaluated for in vitro activity against influenza A and B viruses. The new teicoplanin pseudoaglycon-derived lipoglycopeptides were prepared by coupling one or two side chains to the N-terminus of the glycopeptide core, using various conju...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Szűcs Z,Kelemen V,Le Thai S,Csávás M,Rőth E,Batta G,Stevaert A,Vanderlinden E,Naesens L,Herczegh P,Borbás A

    更新日期:2018-09-05 00:00:00

  • Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents.

    abstract::Several members of the phenylamino-1,4-naphthoquinone series were prepared in order to investigate structure-activity relationships (SAR) and to explore the antitumor effects associated with this scaffold. The cytotoxic effects of the aminoquinones (EC50) against a panel of cancer cell lines (MCF7, DU145 and T24 cells...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Benites J,Valderrama JA,Bettega K,Pedrosa RC,Calderon PB,Verrax J

    更新日期:2010-12-01 00:00:00

  • Salicylanilides as inhibitors of the protein tyrosine kinase epidermal growth factor receptor.

    abstract::A pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase and a putative binding mode of 4-anilinoquinazoline suggest that a salicylic acid function could serve as the pharmacophore replacement of a pyrimidine ring. Superpositions by CAMM of salicylanilid...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Liechti C,Séquin U,Bold G,Furet P,Meyer T,Traxler P

    更新日期:2004-01-01 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

  • Targeting different binding sites in the CFTR structures allows to synergistically potentiate channel activity.

    abstract::Recent evidence shows that combination of correctors and potentiators, such as the drug ivacaftor (VX-770), can significantly restore the functional expression of mutated Cystic Fibrosis Transmembrane conductance Regulator (CFTR), an anion channel which is mutated in cystic fibrosis (CF). The success of these combinat...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Froux L,Elbahnsi A,Boucherle B,Billet A,Baatallah N,Hoffmann B,Alliot J,Zelli R,Zeinyeh W,Haudecoeur R,Chevalier B,Fortuné A,Mirval S,Simard C,Lehn P,Mornon JP,Hinzpeter A,Becq F,Callebaut I,Décout JL

    更新日期:2020-03-15 00:00:00

  • TNF-α and IL-6 inhibitors: Conjugates of N-substituted indole and aminophenylmorpholin-3-one as anti-inflammatory agents.

    abstract::The conjugates obtained by the combination of indole and aminophenyl morpholinone were screened for TNF-α and IL-6 inhibition in microglial cells. Compound 4 was found to be the most potent anti-inflammatory agent as it reduced LPS induced level of inflammatory cytokines TNF-α and IL-6 by 71% and 53%, respectively. A ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Singh P,Kaur S,Sharma A,Kaur G,Bhatti R

    更新日期:2017-11-10 00:00:00

  • Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

    abstract::We have prepared a series of ten 3-arylcoumarin molecules, their respective fac-[Re(CO)3(bpy)L]+ and fac-[Re(CO)3(L⁀L)Br] complexes and tested all compounds for their antimicrobial efficacy. Whereas the 3-arylcoumarin ligands are virtually inactive against the human-associated pathogens with minimum inhibitory concent...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sovari SN,Vojnovic S,Bogojevic SS,Crochet A,Pavic A,Nikodinovic-Runic J,Zobi F

    更新日期:2020-11-01 00:00:00

  • Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities.

    abstract::HIV-1 CA is involved in different stages of the viral replication cycle, performing essential roles in both early (uncoating, reverse transcription, nuclear import, integration) and late events (assembly). Recent efforts have demonstrated HIV-1 CA protein as a prospective therapeutic target for the development of new ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sun L,Huang T,Dick A,Meuser ME,Zalloum WA,Chen CH,Ding X,Gao P,Cocklin S,Lee KH,Zhan P,Liu X

    更新日期:2020-03-15 00:00:00

  • Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease.

    abstract::Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lemes LFN,de Andrade Ramos G,de Oliveira AS,da Silva FMR,de Castro Couto G,da Silva Boni M,Guimarães MJR,Souza INO,Bartolini M,Andrisano V,do Nascimento Nogueira PC,Silveira ER,Brand GD,Soukup O,Korábečný J,Romeiro NC,Cas

    更新日期:2016-01-27 00:00:00

  • Further studies on 2-arylacetamide pyridazin-3(2H)-ones: design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists.

    abstract::Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and tested for FPR agonist activity. The pyridazin-3(2H)-one ring was ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Giovannoni MP,Schepetkin IA,Cilibrizzi A,Crocetti L,Khlebnikov AI,Dahlgren C,Graziano A,Dal Piaz V,Kirpotina LN,Zerbinati S,Vergelli C,Quinn MT

    更新日期:2013-06-01 00:00:00