2,4,5-Tris(alkoxyaryl)imidazoline derivatives as potent scaffold for novel p53-MDM2 interaction inhibitors: Design, synthesis, and biological evaluation.


:Imidazoline-based small molecule inhibitors of p53-MDM2 interaction intended for the treatment of p53 wild-type tumors are the promising structures for design of anticancer drugs. Based on fragment approach we have investigated a key role of substituents in cis-imidazoline core for biological activity of nutlin family compounds. Although the necessity of the substituents in the phenyl rings of cis-imidazoline has been shown, there are no studies in which the replacements of a halogen by other substituents have been investigated. A series of simple cis-imidazoline derivatives containing halogen, hydroxy and alkoxy-substituents were synthesized. The biological activity of the compounds was studied using assays of cytotoxicity (MTT) and p53 level. It was found that the hydroxyl-derivatives were not cytotoxic whereas the alkoxy analogues were the same or more active as halogen-substituted compounds in cell viability test. The synthesized alkoxy derivatives induced an increase of p53 level and did not promote necrotic cell death in the concentration up to 40 µM.


Bioorg Med Chem Lett


Bazanov DR,Pervushin NV,Savitskaya VY,Anikina LV,Proskurnina MV,Lozinskaya NA,Kopeina GS




Has Abstract


2019-08-15 00:00:00














  • Copper dipicolinates as peptidomimetic ligands for the Src SH2 domain.

    abstract::The introduction of copper chelates into peptide mimetics creates the Src SH2 binding ligands and paramagnetic complexes suitable for EPR studies of peptide protein interactions. The dipicolinic acid was attached to SH2 domain targeting fragments by two different linkers. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Schmidt B,Jiricek J,Titz A,Ye G,Parang K

    更新日期:2004-08-16 00:00:00

  • Antiproliferative activity of 2,3-disubstituted indoles toward apoptosis-resistant cancers cells.

    abstract::Many types of cancer, including glioma, melanoma, NSCLC, among others, are resistant to apoptosis induction and poorly responsive to current therapies with propaptotic agents. We describe a series of 2,3-disubstituted indoles, which display cytostatic rather than cytotoxic effects in cancer cells, and serve as a new c...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Magedov IV,Lefranc F,Frolova LV,Banuls LM,Peretti AS,Rogelj S,Mathieu V,Kiss R,Kornienko A

    更新日期:2013-06-01 00:00:00

  • Synthesis and SAR of novel, potent and orally bioavailable benzimidazole inhibitors of poly(ADP-ribose) polymerase (PARP) with a quaternary methylene-amino substituent.

    abstract::Poly(ADP-ribose) polymerases (PARPs) play significant roles in various cellular functions including DNA repair and control of RNA transcription. PARP inhibitors have been demonstrated to potentiate the effect of cytotoxic agents or radiation in a number of animal tumor models. Utilizing a benzimidazole carboxamide sca...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Zhu GD,Gandhi VB,Gong J,Thomas S,Luo Y,Liu X,Shi Y,Klinghofer V,Johnson EF,Frost D,Donawho C,Jarvis K,Bouska J,Marsh KC,Rosenberg SH,Giranda VL,Penning TD

    更新日期:2008-07-15 00:00:00

  • "Cut and combine": an easy membrane-supported combinatorial synthesis technique.

    abstract::A combinatorial synthesis process involving sequential cycles of cutting a membrane support into pieces and combining these into groups and subjecting the groups to simultaneous solid-phase chemical reactions is demonstrated by the rapid assembly of four hundred N-terminally biotinylated, soluble, octameric peptide po...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dittrich F,Tegge W,Frank R

    更新日期:1998-09-08 00:00:00

  • Synthesis, biological evaluation, and molecular docking studies of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives as anticancer agents.

    abstract::A series of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives have been designed, synthesized and evaluated for their potential antiproliferation activity and Aurora-A kinase inhibitory activity. Among all the compounds, compound 10e possessed the most potent biological activity against HCT116 and MCF-7 cell lines...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li X,Lu X,Xing M,Yang XH,Zhao TT,Gong HB,Zhu HL

    更新日期:2012-06-01 00:00:00

  • Structural basis of the dynamic mechanism of ligand binding to cyclooxygenase.

    abstract::Molecular modeling studies performed on the two cyclooxygenase (COX) isozymes suggest that the cavity at the mouth of the active site on the membrane domain that may act as an actual binding site of COX ligands. Actual docking of different inhibitors at this site provides a structural basis to explain the dynamics of ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Llorens O,Perez JJ,Palomer A,Mauleon D

    更新日期:1999-10-04 00:00:00

  • New cytotoxic and anti-inflammatory steroids from the soft coral Klyxum flaccidum.

    abstract::Four new steroids, namely klyflaccisteroids G-J (1-4) were isolated from the Formosan soft coral Klyxum flaccidum. The structures of compounds 1-4 were established by spectral data analysis (IR, MS, 1D and 2D NMR) and comparison of spectral data with those of the related known compounds. Cytotoxicity assay revealed th...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Tseng WR,Huang CY,Tsai YY,Lin YS,Hwang TL,Su JH,Sung PJ,Dai CF,Sheu JH

    更新日期:2016-07-15 00:00:00

  • 3D-QSAR models on clinically relevant K103N mutant HIV-1 reverse transcriptase obtained from two strategic considerations.

    abstract::Clinically relevant Lys103Asn (K103N) mutant frequently observed in HIV-1 reverse transcriptase (RT) confers drug resistance. To obtain useful structural information necessary for targeted-inhibitor design, molecular docking combined with 3D-QSAR CoMFA and CoMSIA was applied to a set of 53 structurally diverse HIV-RT ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: San Juan AA

    更新日期:2008-02-01 00:00:00

  • Preparation, characterization, molecular modeling and in vitro activity of paclitaxel-cyclodextrin complexes.

    abstract::Paclitaxel (PTX) was complexed with beta-cyclodextrin (1), 2,6-dimethyl-beta-cyclodextrin (2) and 2,3,6-trimethyl-beta-cyclodextrin (3). PTX-CYD complexes were characterized both at the solid and liquid states. Experimental findings are in agreement with molecular modeling analysis, which showed different PTX-CYD inte...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Alcaro S,Ventura CA,Paolino D,Battaglia D,Ortuso F,Cattel L,Puglisi G,Fresta M

    更新日期:2002-06-17 00:00:00

  • Synthesis and biological evaluation of two novel DAT-binding technetium complexes containing a piperidine based analogue of cocaine.

    abstract::Two new technetium complexes containing a piperidine template have been synthesized and evaluated as possible leads for the development of dopamine transporter (DAT) imaging agents. Binding data for the corresponding rhenium complexes containing either a monoaminomonoamide (MAMA') or a diaminodithiol (DADT) chelating ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hoepping A,Babich J,Zubieta JA,Johnson KM,Machill S,Kozikowski AP

    更新日期:1999-11-15 00:00:00

  • Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors.

    abstract::The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement generated an analog with similar conformational and physicochemical properties. The series was extended to produce compounds with potent binding affinities and...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Canales E,Carlson JS,Appleby T,Fenaux M,Lee J,Tian Y,Tirunagari N,Wong M,Watkins WJ

    更新日期:2012-07-01 00:00:00

  • Carbonic anhydrase activators: the first X-ray crystallographic study of an adduct of isoform I.

    abstract::The X-ray crystallographic structure for the adduct of an activator with human carbonic anhydrase isozyme I (hCA I) is reported. L-Histidine binds deep within the enzyme active site, participating in a network of hydrogen bonds involving its carboxylate moiety and the zinc-bound water molecule, as well as the imidazol...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Temperini C,Scozzafava A,Supuran CT

    更新日期:2006-10-01 00:00:00

  • Inhibitory mode of 2-acetoxyphenyl alkyl sulfides against COX-1 and COX-2: QSAR analyses.

    abstract::Selective inhibition of cyclooxygenase-2 (COX-2) inhibitors is an important strategy in design of potent anti-inflammatory compounds with significantly reduced side effects. Therefore, QSAR studies of 2-acetoxyphenyl alkyl sulfides were performed using Bioloom, CAChe 6.1, and Dragon 3.0 for the COX-2 and COX-1 inhibit...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Jain HK,Mourya VK,Agrawal RK

    更新日期:2006-10-15 00:00:00

  • Design, synthesis and bioactivity of catechin/epicatechin and 2-azetidinone derived chimeric molecules.

    abstract::A new class of chimeric molecules have been developed. These are based on polyphenols like catechin and epicatechin and monocyclic beta-lactams. The two units are joined via a triazole linker using the 'Click Chemistry' conditions. The compounds showed good to weak antibacterial activity against Escherichia coli as we...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Roy B,Chakraborty A,Ghosh SK,Basak A

    更新日期:2009-12-15 00:00:00

  • Identification of a highly potent and selective CB2 agonist, RQ-00202730, for the treatment of irritable bowel syndrome.

    abstract::Herein we report the identification of a highly potent and selective CB2 agonist, RQ-00202730 (40), obtained by lead optimization of the benzimidazole scaffold. Compound 40 showed strong agonistic activity with an EC50 of 19nM and excellent selectivity (>1300-fold) over the CB1 receptor. Compound 40 displayed a dose d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Iwata Y,Ando K,Taniguchi K,Koba N,Sugiura A,Sudo M

    更新日期:2015-01-15 00:00:00

  • A concise synthesis and antimicrobial activities of 3-polyamino-23,24-bisnorcholanes as steroid-polyamine conjugates.

    abstract::A series of steroid-polyamine conjugates were synthesized and evaluated for their antimicrobial activity. This study was focused on the effect of stereochemistry at the C-3 and C-5 of steroids and types of polyamine at C-3 on activity against various human pathogens. All the conjugates exhibited strong antimicrobial a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kim HS,Khan SN,Jadhav JR,Jeong JW,Jung K,Kwak JH

    更新日期:2011-07-01 00:00:00

  • Synthesis and HIV-1 integrase inhibitory activities of caffeoylglucosides.

    abstract::Caffeoylglucosides, which have a glucose ring as a central linker, were synthesized from methyl D-glucosides, and their anti-HIV-1 activities were tested. Among them, four dicaffeoylglucosides (IC50 = 29.1+/-35.1 microM), 6a, 6b, 9b and 10b, showed HIV-1 integrase inhibitory activity as potent as L-chicoric acid. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Kim SN,Lee JY,Kim HJ,Shin CG,Park H,Lee YS

    更新日期:2000-08-21 00:00:00

  • Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe koreana.

    abstract::Bioassay-guided fractionation of a MeOH extract of the rhizomes of Astilbe koreana (Saxifragaceae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibitory assay, resulted in the isolation of a new triterpene, 3alpha,24-dihydroxyolean-12-en-27-oic acid (4), along with four triterpenes, 3-oxoolean-12-en-27...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Na M,Cui L,Min BS,Bae K,Yoo JK,Kim BY,Oh WK,Ahn JS

    更新日期:2006-06-15 00:00:00

  • Synthesis and antitumor activity of s-tetrazine derivatives.

    abstract::Fifty-five compounds of s-tetrazine derivative including hexahydro-, 1,6-dihydro, 1,4-dihydro-, 1,2-dihydro- and aromatic s-tetrazine were prepared. Their antitumor activities were evaluated in vitro by MTT method for P-388 cell and SRB method for A-549 cell. The results show that there are 9 compounds which in 10(-6)...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Hu WX,Rao GW,Sun YQ

    更新日期:2004-03-08 00:00:00

  • Diaminopyrimidine and diaminopyridine 5-HT7 ligands.

    abstract::The present studies have identified a series of diaminopyrimidines and diaminopyridines as novel 5-HT(7) receptor ligands. Three regiosiomeric classes of pyrimidines and four regioisomeric classes of pyridines were synthesized and analyzed for binding to the 5-HT(7) receptor. The 5-HT(7) binding affinities of differen...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Denhart DJ,Purandare AV,Catt JD,King HD,Gao A,Deskus JA,Poss MA,Stark AD,Torrente JR,Johnson G,Mattson RJ

    更新日期:2004-08-16 00:00:00

  • Structure-activity relationship of linear peptide Bu-His6-DPhe7-Arg8-Trp9-Gly10-NH2 at the human melanocortin-1 and -4 receptors: DPhe7 and Trp9 substitution.

    abstract::A series of pentapeptides, based on hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2)), was prepared in which either DPhe(7) or Trp(9) residue was systematically substituted. A number of interesting DPhe surrogates (D-Thi, D-3-CF(3)Phe, D-2-Nal and D-3,4-diClPhe) as well as Trp surrogates (2-Na...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Danho W,Swistok J,Cheung AW,Kurylko G,Franco L,Chu XJ,Chen L,Yagaloff K

    更新日期:2003-02-24 00:00:00

  • POMA analyses as new efficient bioinformatics' platform to predict and optimise bioactivity of synthesized 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues.

    abstract::A series of 43, 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide/carbothioamide analogues (D01-D43) were analysed using Petra, Osiris, Molinspiration and ALOGPS (POMA) to identify pharmacophore, toxicity prediction, lipophilicity and bioactivity. All the compounds were evaluated for anti-HIV activity. 3-(4-Chloroph...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ahsan MJ,Govindasamy J,Khalilullah H,Mohan G,Stables JP

    更新日期:2012-12-01 00:00:00

  • Isatin derivatives with activity against apoptosis-resistant cancer cells.

    abstract::In a search of small molecules active against apoptosis-resistant cancer cells, a series of isatin-based heterocyclic compounds were synthesized and found to inhibit proliferation of cancer cell lines resistant to apoptosis. The synthesis of these compounds involved a condensation of commercially available, active met...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Evdokimov NM,Magedov IV,McBrayer D,Kornienko A

    更新日期:2016-03-15 00:00:00

  • Discovery and structure-activity relationships of pentanedioic acid diamides as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type I.

    abstract::Benzylamides of pentanedioic acid were identified as inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) by high-throughput screening. Optimisation to 2-adamantyl amides yielded inhibitors with single digit nanomolar IC(50)s on the 11beta-HSD1 human isoform. The hydroxy adamantyl amide lead compound...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Roche D,Carniato D,Leriche C,Lepifre F,Christmann-Franck S,Graedler U,Charon C,Bozec S,Doare L,Schmidlin F,Lecomte M,Valeur E

    更新日期:2009-05-15 00:00:00

  • Exploration of GGTase-I substrate requirements. Part 1: Synthesis and biochemical evaluation of novel aryl-modified geranylgeranyl diphosphate analogs.

    abstract::Protein geranylgeranylation is a type of post-translational modification that aids in the localization of proteins to the plasma member where they elicit cellular signals. To better understand the isoprenoid requirements of GGTase-I, a series of aryl-modified geranylgeranyl diphosphate analogs were synthesized and scr...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Temple KJ,Wright EN,Fierke CA,Gibbs RA

    更新日期:2016-08-01 00:00:00

  • Design and evaluation of novel oxadiazole derivatives as potential prostate cancer agents.

    abstract::Various 1,3,4-oxadiazole derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cell lines. Most of the compounds showed promising activity. Among them, compounds...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Mochona B,Qi X,Euynni S,Sikazwi D,Mateeva N,Soliman KF

    更新日期:2016-06-15 00:00:00

  • Design, synthesis and docking study of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as inhibitors of protein tyrosine phosphatase 1B.

    abstract::A series of novel 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives was designed, and synthesized based on our previous studies. Also their activities were evaluated as competitive inhibitors of protein tyrosine phosphatase 1B (PTP1B). Compounds 6d-6g, 7b, 7c, 7e, 7j, 7k, 7m, 14b and 14e-14f showed potent ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Wang Z,Liu Z,Lee W,Kim SN,Yoon G,Cheon SH

    更新日期:2014-08-01 00:00:00

  • Radical-scavenging properties of ferrocenyl chalcones.

    abstract::The radical-scavenging capacities of ferrocenyl group and phenolic hydroxyl group in ferrocenyl chalcone were identified in this work. 1,1'-Diacetylferrocene was applied to condense with benzaldehyde, vanillin, and protocatechualdehyde to produce ferrocenyl chalcones, which were employed to interact with 2,2'-azinobis...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nabi G,Liu ZQ

    更新日期:2011-02-01 00:00:00

  • Synthesis and SAR study of tricyclic sulfones as γ-secretase inhibitors: C-6 and C-8 positions.

    abstract::SAR exploration at C-6 and C-8 positions of the tricyclic sulfone series was carried out. Several functional groups were found to be well tolerated at C-6 and C-8 positions. Selective combination of C-6 and C-8 modification resulted in new tricyclic sulfone analogs with efficacy in in vivo mouse Aβ(40) lowering model....

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Su J,Tang H,McKittrick BA,Xu R,Clader JW,Greenlee WJ,Hyde L,Zhang L

    更新日期:2011-06-01 00:00:00

  • Dopamine/serotonin receptor ligands. Part 15: Oxygenation of the benz-indolo-azecine LE 300 leads to novel subnanomolar dopamine D1/D5 antagonists.

    abstract::Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of 1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the aff...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Enzensperger C,Kilian S,Ackermann M,Koch A,Kelch K,Lehmann J

    更新日期:2007-03-01 00:00:00