Synthesis, evaluation and 3D QSAR analysis of novel estradiol-RGD octapeptide conjugates with oral anti-osteoporosis activity.


:To enhance the potency, reduce the side effects and improve oral property of estradiol in estrogen replacement therapy (ERT), 6 novel estradiol-RGD octapeptide conjugates have been prepared. In an ovariectomized mouse osteoporotic model, at an oral dosage of 110.3 nmol/kg per day, their anti-osteoporosis activity was significantly higher than that of estradiol and estradiol-RGD tetrapeptide conjugates, and their risks of thrombogenesis and endometrial hyperplasia were significantly lower than that of estradiol and estradiol-RGD tetrapeptide conjugates. Using QSAR module of Cerius2, the 3D QSAR was performed for both femur weights and femur ash weights of estradiol-RGD peptide conjugates receiving mice. The r(2) of the 3D QSAR equations up to 0.995 and 0.988 indicates that they are capable of predicting a comparatively exact anti-osteoporosis activity for a conjugate.


Eur J Med Chem


Liu J,Zhang X,Zhao M,Peng S




Has Abstract


2009-04-01 00:00:00














  • Synthesis and neuromuscular blocking activity of 16beta-piperidinosteroidal derivatives.

    abstract::The synthesis and pharmacological profiles of some new steroidal mono- and bisquaternary ammonium derivatives have been described. The compounds featured have been conceptually derived structurally from two lead structures: pancuronium bromide 1 and chandonium iodide 2. In vitro and in vivo neuromuscular blocking stud...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Jindal DP,Piplani P,Fajrak H,Prior C,Marshall IG

    更新日期:2001-02-01 00:00:00

  • Optimization of novel oxidative DIMs as Nur77 modulators of the Nur77-Bcl-2 apoptotic pathway.

    abstract::Nur77, an orphan nuclear receptor, is a member of the nuclear receptor superfamily. Nur77 plays important roles in various biological processes. Previously we reported that BI1071(DIM-C-pPhCF3+MeSO3-), an oxidized form and methanesulfonate salt of (4-CF3-Ph-C-DIM), can modulate Nur77's non-genomic apoptotic pathway th...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tu X,Chen X,Zhang D,Gao M,Liang J,Bao G,Zhang J,Peng S,Zhang X,Zeng Z,Su Y

    更新日期:2021-02-05 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

  • Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates.

    abstract::A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piper...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Dias Viegas FP,de Freitas Silva M,Divino da Rocha M,Castelli MR,Riquiel MM,Machado RP,Vaz SM,Simões de Lima LM,Mancini KC,Marques de Oliveira PC,Morais ÉP,Gontijo VS,da Silva FMR,D'Alincourt da Fonseca Peçanha D,Castro NG,N

    更新日期:2018-03-10 00:00:00

  • New transition metal ion complexes with benzimidazole-5-carboxylic acid hydrazides with antitumor activity.

    abstract::Metal complexes of 2-methyl-1H-benzimidazole-5-carboxylic acid hydrazide (4a; L(1)) and its Schiff base 2-methyl-N-(propan-2-ylidene)-1H-benzimidazole-5-carbohydrazide (5a; L(2)) with transition metal ions e.g., copper, silver, nickel, iron and manganese were prepared. The complexes formed were 1:1 or 1:2 M:L complexe...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Galal SA,Hegab KH,Kassab AS,Rodriguez ML,Kerwin SM,el-Khamry AM,el-Diwani HI

    更新日期:2009-04-01 00:00:00

  • Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of type 2 diabetes mellitus.

    abstract::The rising incidence of diabetes and confines allied with clinical therapies emphasized the need to explore new molecular targets to develop novel, effective and safer antihyperglycemic agents. Excessive endogenous glucose production by gluconeogenesis is a primary determinant of hyperglycemia in patients with type 2 ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Kaur R,Dahiya L,Kumar M

    更新日期:2017-12-01 00:00:00

  • Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.

    abstract::Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective g...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Deck LM,Hunsaker LA,Vander Jagt TA,Whalen LJ,Royer RE,Vander Jagt DL

    更新日期:2018-01-01 00:00:00

  • Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: design, synthesis, biological evaluation, and docking studies.

    abstract::We report the design and synthesis of a series of dipeptide-type inhibitors with novel P3 scaffolds that display potent inhibitory activity against SARS-CoV 3CLpro. A docking study involving binding between the dipeptidic lead compound 4 and 3CLpro suggested the modification of a structurally flexible P3 N-(3-methoxyp...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Thanigaimalai P,Konno S,Yamamoto T,Koiwai Y,Taguchi A,Takayama K,Yakushiji F,Akaji K,Chen SE,Naser-Tavakolian A,Schön A,Freire E,Hayashi Y

    更新日期:2013-10-01 00:00:00

  • The discovery of new potent non-peptide Angiotensin II AT1 receptor blockers: a concise synthesis, molecular docking studies and biological evaluation of N-substituted 5-butylimidazole derivatives.

    abstract::A convenient and facile synthesis, in silico docking studies and in vitro biological evaluation of N-substituted 5-butylimidazole derivatives as potent Angiotensin II (ANG II) receptor type 1 (AT1) blockers (ARBs) has been reported in the current study. Our efforts have been directed towards the development of an effi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Agelis G,Resvani A,Durdagi S,Spyridaki K,Tůmová T,Slaninová J,Giannopoulos P,Vlahakos D,Liapakis G,Mavromoustakos T,Matsoukas J

    更新日期:2012-09-01 00:00:00

  • Cyclooxygenase-1/2 (COX-1/COX-2) and 5-lipoxygenase (5-LOX) inhibitors of the 6,7-diaryl-2,3-1H-dihydropyrrolizine type.

    abstract::A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metaboli...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Ulbrich H,Fiebich B,Dannhardt G

    更新日期:2002-12-01 00:00:00

  • Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents.

    abstract::A series of forty different pyrazole containing benzimidazole hybrids (6-45) have been designed, synthesized and evaluated for their potential anti-proliferative activity against three human tumor cell lines - lung (A549), breast (MCF-7), and cervical (HeLa). Some of the compounds, specifically 9, 17, and 28, showed p...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Reddy TS,Kulhari H,Reddy VG,Bansal V,Kamal A,Shukla R

    更新日期:2015-08-28 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

  • Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models.

    abstract::Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Gonzalez G,Hodoň J,Kazakova A,D'Acunto CW,Kaňovský P,Urban M,Strnad M

    更新日期:2021-01-16 00:00:00

  • Optimisation of correlation weights of SMILES invariants for modelling oral quail toxicity.

    abstract::The SMILES (simplified molecular input line entry system) nomenclature was used to elucidate the molecular structure in constructing the quantitative structure-property/activity relationships (QSPR/QSAR) for predicting quail toxicity after oral exposure. The presence of chemical elements in different electronic states...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Toropov AA,Benfenati E

    更新日期:2007-05-01 00:00:00

  • Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I.

    abstract::A new series of 2-substituted imino-3-substituted-5- heteroarylidene-1,3-thiazolidine-4-ones as the potent bidentate PTP1B inhibitors were designed and synthesized in this paper. All of the new compounds were characterized and identified by spectra analysis. The biological screening test against PTP1B showed that some...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Meng G,Zheng M,Wang M,Tong J,Ge W,Zhang J,Zheng A,Li J,Gao L,Li J

    更新日期:2016-10-21 00:00:00

  • Second-generation sulfonamide inhibitors of D-glutamic acid-adding enzyme: activity optimisation with conformationally rigid analogues of D-glutamic acid.

    abstract::D-Glutamic acid-adding enzyme (MurD) catalyses the essential addition of d-glutamic acid to the cytoplasmic peptidoglycan precursor UDP-N-acetylmuramoyl-l-alanine, and as such it represents an important antibacterial drug-discovery target enzyme. Based on a series of naphthalene-N-sulfonyl-d-Glu derivatives synthesise...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sosič I,Barreteau H,Simčič M,Sink R,Cesar J,Zega A,Grdadolnik SG,Contreras-Martel C,Dessen A,Amoroso A,Joris B,Blanot D,Gobec S

    更新日期:2011-07-01 00:00:00

  • Synthesis of Abyssinone II and related compounds as potential chemopreventive agents.

    abstract::A facile and efficient approach to the synthesis of prenylated flavonoids as potential chemopreventive agents has been described. This features the synthesis of prenyl halide, prenylation of p-hydroxybenzaldehyde, formation of prenylated polyhydroxychalcone and cyclization of prenylated polyhydroxychalcone to flavanon...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Moriarty RM,Grubjesic S,Surve BC,Chandersekera SN,Prakash O,Naithani R

    更新日期:2006-02-01 00:00:00

  • Antihyperglycemic and antihyperlipidemic activities of 2-(4-[(2-hydroxybenzyl) amino]-phenyl amino-methyl)-phenol in STZ induced diabetic rats.

    abstract::Oral administration of 2-(4-[(2-hydroxybenzyl) amino]-phenyl amino-methyl)-phenol (HBPMP) (30 mg/kg) to Streptozotocin (STZ) rats produced significant antidiabetic activity after 6 h of HBPMP administration. Treatment of the STZ rats with HBPMP (30 mg/kg/day) for 30 days resulted in a significant decrease in their Fas...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sirasanagandla S,Kasetti RB,Shaik AN,Natava R,Surtineni VP,Cirradur SR,Chippada A

    更新日期:2013-08-01 00:00:00

  • Synthesis and preliminary in vitro biological evaluation of 7α-testosterone-chlorambucil hybrid designed for the treatment of prostate cancer.

    abstract::The synthesis of 7α-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7α-allyltesto...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Bastien D,Hanna R,Leblanc V,Asselin É,Bérubé G

    更新日期:2013-06-01 00:00:00

  • Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives.

    abstract::A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different t...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Guimarães KG,de Freitas RP,Ruiz AL,Fiorito GF,de Carvalho JE,da Cunha EF,Ramalho TC,Alves RB

    更新日期:2016-03-23 00:00:00

  • Peroxisome proliferator-activated receptor-γ mediates the anti-inflammatory effect of 3-hydroxy-4-pyridinecarboxylic acid derivatives: synthesis and biological evaluation.

    abstract::Seven 3-hydroxy-4-pyridinecarboxylic acid derivatives (HPs), aza-analogues of salicylic acid and structurally close to other potent inflammatory pyridine compounds such as aminopyridinylmethanols and aminopyridinamines, were synthesized, and their anti-inflammatory activity was evaluated. The synthesis was performed b...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Brun P,Dean A,Di Marco V,Surajit P,Castagliuolo I,Carta D,Ferlin MG

    更新日期:2013-04-01 00:00:00

  • Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as cannabinoid receptor ligands.

    abstract::A series of N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as new ligands of the human recombinant receptor hCB1. n-Alkyl carboxamides brought out different SARs from the branched subgroup. Unsubstituted pyrrole derivatives bearing a tert-alkyl chain at the 3-carboxamide nitrogen showed ...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Silvestri R,Ligresti A,La Regina G,Piscitelli F,Gatti V,Lavecchia A,Brizzi A,Pasquini S,Allarà M,Fantini N,Carai MA,Bigogno C,Rozio MG,Sinisi R,Novellino E,Colombo G,Di Marzo V,Dondio G,Corelli F

    更新日期:2010-12-01 00:00:00

  • Identification of novel benzothiopyranone compounds against Mycobacterium tuberculosis through scaffold morphing from benzothiazinones.

    abstract::In this study, three novel series of benzoxazinone, benzothiopyranone and benzopyranone derivatives were designed through scaffold morphing from benzothiazinones to target DprE1. All compounds were evaluated for their in vitro activities against Mycobacterium tuberculosis and cytotoxicity against Vero cell line. Among...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Li P,Wang B,Zhang X,Batt SM,Besra GS,Zhang T,Ma C,Zhang D,Lin Z,Li G,Huang H,Lu Y

    更新日期:2018-12-05 00:00:00

  • Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors.

    abstract::5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vbl cervix and MCF-7/...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mahal K,Biersack B,Schruefer S,Resch M,Ficner R,Schobert R,Mueller T

    更新日期:2016-08-08 00:00:00

  • Synthesis, antitubercular activity and docking study of novel cyclic azole substituted diphenyl ether derivatives.

    abstract::The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clin...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kini SG,Bhat AR,Bryant B,Williamson JS,Dayan FE

    更新日期:2009-02-01 00:00:00

  • Design, synthesis and in vitro anti-influenza A virus evaluation of novel quinazoline derivatives containing S-acetamide and NH-acetamide moieties at C-4.

    abstract::It is an urgent need to develop more effective anti-influenza agents due to the emergence of highly pathogenic and drug-resistant influenza viruses. Herein, a series of 2,4-disubstituted quinazoline derivatives were designed, synthesized and their antiviral activities against influenza A virus were evaluated. Nine com...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang G,Wang M,Zhao J,Wang Y,Zhu M,Wang J,Cen S,Wang Y

    更新日期:2020-11-15 00:00:00

  • Design, synthesis and structure-activity relationship of phthalimides endowed with dual antiproliferative and immunomodulatory activities.

    abstract::The present work reports the synthesis and evaluation of the antitumour and immunomodulatory properties of new phthalimides derivatives designed to explore molecular hybridization and bioisosterism approaches between thalidomide, thiosemicarbazone, thiazolidinone and thiazole series. Twenty-seven new molecules were as...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cardoso MV,Moreira DR,Oliveira Filho GB,Cavalcanti SM,Coelho LC,Espíndola JW,Gonzalez LR,Rabello MM,Hernandes MZ,Ferreira PM,Pessoa C,Alberto de Simone C,Guimarães ET,Soares MB,Leite AC

    更新日期:2015-01-01 00:00:00

  • Desing and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death.

    abstract::Chagas disease, caused by the kinetoplastid protozoan parasite Trypanosoma cruzi, remains a relevant cause of illness and premature death and it is estimated that 6 million to 7 million people are infected worldwide. Although chemotherapy options are limited presenting serious problems, such as low efficacy and high t...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: da Silva EB,Oliveira E Silva DA,Oliveira AR,da Silva Mendes CH,Dos Santos TA,da Silva AC,de Castro MC,Ferreira RS,Moreira DR,Cardoso MV,de Simone CA,Pereira VR,Leite AC

    更新日期:2017-04-21 00:00:00

  • A novel orally active inhibitor of HLE.

    abstract::Human leukocyte elastase (HLE) is a serine proteinase, capable of degrading a variety of structural matrix proteins. SSR69071 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methoxy]-9-(2-piperidin-1-ylethoxy)-4H-pyrido[1,2-a]pyrimidin-4-one was selected as a novel orally active HLE inhibitor f...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Varga M,Kapui Z,Bátori S,Nagy LT,Vasvári-Debreczy L,Mikus E,Urbán-Szabó K,Arányi P

    更新日期:2003-04-01 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