Rhodium(II) acetate-catalyzed stereoselective synthesis, SAR and anti-HIV activity of novel oxindoles bearing cyclopropane ring.


:Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having trans relationship with respect to carbonyl of lactam moiety and functional group on the cyclopropane ring, was the major product in all cases along with a small amount of cis and methylene products. The trans isomers interacted well with HIV-1 RT through H-bonding with amino acids, like Lys101, Lys103, His235, Tyr318, constituting the non-nucleoside inhibitor binding pocket (NNIBP) during docking experiments. However, the compounds showed very little activity when subjected to in vitro anti-HIV-1 screening using β-galactosidase assay (TZM-bl cells) and GFP quantification (CEM-GFP cells). The very low level of in vitro HIV inhibition, in comparison to predicted EC(50) values on the basis of computational studies, during CEM-GFP screening using AZT as positive control indicated that probably the HIV RT is not the viral target and the molecules work through some different mechanism.


Eur J Med Chem


Kumari G,Nutan,Modi M,Gupta SK,Singh RK




Has Abstract


2011-04-01 00:00:00














  • QSAR study on tetrahydroquinoline analogues as plasmodium protein farnesyltransferase inhibitors: a comparison of rationales of malarial and mammalian enzyme inhibitory activities for selectivity.

    abstract::The quantitative structure-activity relationships of Plasmodium falciparum and Rat protein farnesyltransferase (PFT) inhibitory activities of 6-cyano-1-(3-methyl-3H-imidazoly-4-ylmethyl)-3-substituted-1,2,3,4-tetrahydroquinoline (THQ) analogues are investigated in order to explore the similarities/deviations between t...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gupta MK,Prabhakar YS

    更新日期:2008-12-01 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

  • Vocational training for medicinal chemists: views from industry.

    abstract::The Medicinal Chemistry Section of IUPAC sent a questionnaire regarding academic training for medicinal chemists to major research pharmaceutical companies in various countries in July 1992 and again in July 1993. A total of 102 replies were received from 65 companies, mainly from Germany, Italy, Japan, the UK and the...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Busse W,Ganellin C,Mitscher L

    更新日期:1996-01-01 00:00:00

  • Model for high-throughput screening of drug immunotoxicity--study of the anti-microbial G1 over peritoneal macrophages using flow cytometry.

    abstract::Quantitative Structure-Activity (mt-QSAR) techniques may become an important tool for prediction of cytotoxicity and High-throughput Screening (HTS) of drugs to rationalize drug discovery process. In this work, we train and validate by the first time mt-QSAR model using TOPS-MODE approach to calculate drug molecular d...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tenorio-Borroto E,Peñuelas-Rivas CG,Vásquez-Chagoyán JC,Castañedo N,Prado-Prado FJ,García-Mera X,González-Díaz H

    更新日期:2014-01-24 00:00:00

  • Synthesis of oleanolic acid dimers linked at C-28 and evaluation of anti-tumor activity.

    abstract::Five dimeric oleanolic acids linked at C-28 by 1,6-hexanediamine, or built around the carbon chains of varying lengths between two carboxyl groups were synthesized, to investigate the effect of internal spacer length and species upon the stereochemical features and anti-tumor activity of the resultant bis-oleanolic ac...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cheng KG,Su CH,Yang LD,Liu J,Chen ZF

    更新日期:2015-01-07 00:00:00

  • Newly designed organotin(IV) carboxylates with peptide linkage: Synthesis, structural elucidation, physicochemical characterizations and pharmacological investigations.

    abstract::Fourteen new organotin(IV) carboxylate complexes with peptide linkage of (2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid) were successfully synthesized and characterized by elemental analyses, FT-IR, NMR (1H, 13C and 119Sn) and single crystal X-ray techniques. FT-IR results of the sodium salt of 2-(4-methoxy-2-nitro...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sirajuddin M,McKee V,Tariq M,Ali S

    更新日期:2018-01-01 00:00:00

  • Structure-activity relationship studies and pharmacological characterization of N5-heteroarylalkyl-substituted-2-(2-furanyl)thiazolo[5,4-d]pyrimidine-5,7-diamine-based derivatives as inverse agonists at human A2A adenosine receptor.

    abstract::This paper describes the synthesis and characterization of N5-(hetero)arylalkyl-substituted-thiazolo [5,4-d]pyrimidine-5,7-diamine derivatives (4-19) as novel human (h) A2A adenosine receptor (AR) inverse agonists. Competition binding and cyclic AMP assays indicate that the examined compounds behave as hA2A AR inverse...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Varano F,Catarzi D,Vincenzi F,Falsini M,Pasquini S,Borea PA,Colotta V,Varani K

    更新日期:2018-07-15 00:00:00

  • Design, synthesis and characterization of peptidomimetic conjugate of BODIPY targeting HER2 protein extracellular domain.

    abstract::Among the EGFRs, HER2 is a major heterodimer partner and also has important implications in the formation of particular tumors. Interaction of HER2 protein with other EGFR proteins can be modulated by small molecule ligands and, hence, these protein-protein interactions play a key role in biochemical reactions related...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Banappagari S,McCall A,Fontenot K,Vicente MG,Gujar A,Satyanarayanajois S

    更新日期:2013-07-01 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 biological evaluation of (1,2,4)triazole[4,3-a]pyridine derivatives as potential therapeutic agents for concanavalin A-induced hepatitis.

    abstract::A series of (1,2,4)triazole[4,3-a]pyridine (TZP) derivatives have been designed and synthesized. Compound 8d was identified as having the most potent inhibitory activity on NO release in response to lipopolysaccharide (LPS) stimulation and inhibition of the migration induced by MCP-1 protein on RAW264.7 macrophages. B...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Shi Y,Wang Q,Rong J,Ren J,Song X,Fan X,Shen M,Xia Y,Wang N,Liu Z,Hu Q,Ye T,Yu L

    更新日期:2019-10-01 00:00:00

  • Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids.

    abstract::A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid pa...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Nepali K,Sharma S,Sharma M,Bedi PM,Dhar KL

    更新日期:2014-04-22 00:00:00

  • Modification of the length and structure of the linker of N(6)-benzyladenosine modulates its selective antiviral activity against enterovirus 71.

    abstract::Very recently, we demonstrated that N(6)-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. The present study is devoted to the structure optimization of another natural compound: N(6)-benzyladenosine. We mainly focused on the explor...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Drenichev MS,Oslovsky VE,Sun L,Tijsma A,Kurochkin NN,Tararov VI,Chizhov AO,Neyts J,Pannecouque C,Leyssen P,Mikhailov SN

    更新日期:2016-03-23 00:00:00

  • Structure--activity relationship studies of novel arylsulfonylimidazolidinones for their anticancer activity.

    abstract::To define the SAR, a series of novel N-arylsulfonylimidazolidinone derivatives were evaluated for their in vitro anticancer activity against five human tumor cell lines, including A549, COLO205, KATO III, K562, SK-OV-3 and murine leukemia (P288D1) cell line. Among them, N-(2-chloroacetyl)-6-(2-oxo-4-phenylimidazolidin...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Subramanian S,Kim NS,Thanigaimalai P,Sharma VK,Lee KC,Kang JS,Kim HM,Jung SH

    更新日期:2011-08-01 00:00:00

  • Synthesis, analgesic and anti-inflammatory activities evaluation of some bi-, tri- and tetracyclic condensed pyrimidines.

    abstract::Novel series of bicyclic pyrrolo[1,2-c]pyrimidines 3a-g, 5, 6a, b, and 7a, b, tricyclic pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines 8a-c, 9a-g, 13a-c, 17, 18a, b, 19, 20a,b and 21 and tetracyclic condensed pyrimidines 14, 22 and 23 were synthesized through different chemical reactions. Structures of all synthesized pyrim...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Amin KM,Hanna MM,Abo-Youssef HE,George RF

    更新日期:2009-11-01 00:00:00

  • Design and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells.

    abstract::Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyr...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Garamvölgyi R,Dobos J,Sipos A,Boros S,Illyés E,Baska F,Kékesi L,Szabadkai I,Szántai-Kis C,Kéri G,Őrfi L

    更新日期:2016-01-27 00:00:00

  • Synthesis and evaluation of novel hybrids β-carboline-4-thiazolidinones as potential antitumor and antiviral agents.

    abstract::A series of novel hybrids β-carboline-4-thiazolidinones were synthesized and evaluated for their in vitro antitumor activity against human cancer cell lines and for antiviral activity towards Herpes simplex virus type-1 (HSV-1). From the N'-(2-ylidene-4-thiazolidinone)-β-carboline-3-carbohydrazide series (9-11), compo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Barbosa VA,Baréa P,Mazia RS,Ueda-Nakamura T,Costa WFD,Foglio MA,Goes Ruiz ALT,Carvalho JE,Vendramini-Costa DB,Nakamura CV,Sarragiotto MH

    更新日期:2016-11-29 00:00:00

  • Synthesis by microwave irradiation and binding properties of novel 5-HT(1A) receptor ligands.

    abstract::This work reports the synthesis by microwave irradiation and the binding tests on the 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptors of new substituted piperazines in order to identify selective ligands for 5-HT(1A) subtype receptor. Conventional heating and microwave irradiation of the reactions was compared. Synthesis by...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Caliendo G,Fiorino F,Perissutti E,Severino B,Gessi S,Cattabriga E,Borea PA,Santagada V

    更新日期:2001-11-01 00:00:00

  • Synthesis and biological evaluation of fatty acids conjugates bearing cyclopentadienyl-donors incorporated [(99m)Tc/Re(CO)3]+ for myocardical imaging.

    abstract::Four (99m)Tc-labeled fatty acid analogs, 1b, 2b, 3b, 4b were synthesized by a double ligand transfer reaction and theirs potential were investigated. The radiochemical yield of the radiotracers was from 11.7% to 30.3% (no decay corrected). Those compounds were found to be chemically stable when incubated in SD rat ser...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zeng H,Zhang H

    更新日期:2014-01-24 00:00:00

  • Biotransformation of LASSBio-579 and pharmacological evaluation of p-hydroxylated metabolite a N-phenylpiperazine antipsychotic lead compound.

    abstract::Using a combination of docking and molecular dynamics simulations, we predicted that p-hydroxylation by CYP1A2 would be the main metabolic pathway for the 1-[1-(4-chlorophenyl)-1H-4pyrazolylmethyl] phenylhexahydropiperazine, LASSBio-579 (3). As the result of a screening process with strains of filamentous fungi, Cunni...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gomes TF,Pompeu TE,Rodrigues DA,Noël F,Menegatti R,Andrade CH,Sabino JR,Gil ES,Dalla Costa T,Betti AH,Antonio CB,Rates SM,Fraga CA,Barreiro EJ,de Oliveira V

    更新日期:2013-04-01 00:00:00

  • Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines.

    abstract::Development of novel anticancer drugs is inevitable to improve treatment of cancers. In this study, novel derivatives of indoline and morpholine were synthesized and tested for their cytotoxic effects on osteosarcoma and Human Embryonic Kidney cells. To characterize cytotoxicity and the mechanism of cell death, we use...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Doan P,Karjalainen A,Chandraseelan JG,Sandberg O,Yli-Harja O,Rosholm T,Franzen R,Candeias NR,Kandhavelu M

    更新日期:2016-09-14 00:00:00

  • Dibenzo[1,4,5]thiadiazepine: a hardly-known heterocyclic system with neuroprotective properties of potential usefulness in the treatment of neurodegenerative diseases.

    abstract::In this work we describe a new family of dibenzo[1,4,5]thiadiazepines (2-12) that showed an interesting in vitro biological profile, namely neuroprotective and antioxidant properties, as well as blockade of cytosolic calcium entry. They showed no cytotoxic effects and the majority were predicted as CNS-permeable compo...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: González-Muñoz GC,Arce MP,Pérez C,Romero A,Villarroya M,López MG,Conde S,Rodríguez-Franco MI

    更新日期:2014-06-23 00:00:00

  • Spirostanols obtained by cyclization of pseudosaponin derivatives and comparison of anti-platelet agglutination activities of spirostanol glycosides.

    abstract::Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3 and 4, respectively, with alcoholic KOH, followed by acidification with acetic acid, gave spirostanols 20 and 22 having iso type F rings as major products. ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tobari A,Teshima M,Koyanagi J,Kawase M,Miyamae H,Yoza K,Takasaki A,Nagamura Y,Saito S

    更新日期:2000-05-01 00:00:00

  • Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents.

    abstract::To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the deriv...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Yu H,Hou Z,Tian Y,Mou Y,Guo C

    更新日期:2018-05-10 00:00:00

  • Antimycobacterial activity of natural products and synthetic agents: pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of Mycobacterium tuberculosis.

    abstract::Various classes of natural products and synthetic compounds were tested against reference strains and clinical multidrug resistant isolates of Mycobacterium tuberculosis. Vermelhotin (19), a natural tetramic acid from fungi, was the most active toward clinical MDR TB isolates (MIC 1.5-12.5 μg/mL). Synthetic compounds ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ganihigama DU,Sureram S,Sangher S,Hongmanee P,Aree T,Mahidol C,Ruchirawat S,Kittakoop P

    更新日期:2015-01-07 00:00:00

  • Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents.

    abstract::By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI₅₀...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chen TC,Yu DS,Huang KF,Fu YC,Lee CC,Chen CL,Huang FC,Hsieh HH,Lin JJ,Huang HS

    更新日期:2013-11-01 00:00:00

  • Synthesis and antitumor evaluation of novel diarylsulfonylurea derivatives: molecular modeling applications.

    abstract::Some new ethyl 2-[3-(4-unsubstituted or 4-substituted phenylsufonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylates 3a-c, 2-[3-(phenylsulfonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbohydrazides 4a-f, 3-phenylsulfonyl-6,7,8,9-tetrahydro-5H-cyclohepta[1',2':4,5]thieno[2,3-d]pyrimi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: El-Sherbeny MA,Abdel-Aziz AA,Ahmed MA

    更新日期:2010-02-01 00:00:00

  • Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A: High-throughput virtual screening, synthesis and biological validation.

    abstract::Most cancer cells feature an altered glucose metabolism from oxidative phosphorylation to cytoplasmic glycolysis. Pyruvate dehydrogenase kinases (PDKs) and lactate dehydrogenase A (LDHA) play crucial roles in promotion of glycolysis, thus the inhibition of both enzymes is considered a promising strategy for developing...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Xiang S,Huang D,He Q,Li J,Tam KY,Zhang SL,He Y

    更新日期:2020-10-01 00:00:00

  • Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer's disease.

    abstract::A series of fifteen acetylcholinesterase inhibitors were designed and synthesised based upon the previously identified lead compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (5) which showed good inhibitory activity (IC50 0.03 ± 0.07 μM) against acetylcholinesterase. A series of c...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: van Greunen DG,Johan van der Westhuizen C,Cordier W,Nell M,Stander A,Steenkamp V,Panayides JL,Riley DL

    更新日期:2019-10-01 00:00:00

  • Optimization of pharmacokinetic properties by modification of a carbazole-based cannabinoid receptor subtype 2 (CB2) ligand.

    abstract::Recently, the development of the fluorinated PET tracer [18F]1a for imaging of CB2 receptors in the central nervous system was reported. [18F]1a showed high CB2 affinity and selectivity over the CB1 subtype, but rapid biotransformation in mice. In addition to the amide hydrolysis, oxidative N-dealkylation and carbazol...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Heimann D,Börgel F,de Vries H,Bachmann K,Rose VE,Frehland B,Schepmann D,Heitman LH,Wünsch B

    更新日期:2018-01-01 00:00:00

  • Structure-based design, semi-synthesis and anti-inflammatory activity of tocotrienolic amides as 5-lipoxygenase inhibitors.

    abstract::Inflammation contributes to the development of various pathologies, e.g. asthma, cardiovascular diseases, some types of cancer, and metabolic disorders. Leukotrienes (LT), biosynthesized from arachidonic acid by 5-lipoxygenase (5-LO), constitute a potent family of pro-inflammatory lipid mediators. δ-Garcinoic acid (δ-...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Dinh CP,Ville A,Neukirch K,Viault G,Temml V,Koeberle A,Werz O,Schuster D,Stuppner H,Richomme P,Helesbeux JJ,Séraphin D

    更新日期:2020-09-15 00:00:00