Abstract:
:Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses. Here, we evaluated the carrier and antitumor activity of novel hemocyanins with documented immunogenicity obtained from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH), coupled through sulfo-SMCC to P10, a mimetic peptide of GD2, the major ganglioside constituent of neuroectodermal tumors, and incorporating AddaVax as an adjuvant. The humoral immune responses of mice showed that CCH-P10 and FLH-P10 conjugates elicited specific IgM and IgG antibodies against P10 mimotope, similar to those obtained with KLH-P10, which was used as a positive control. The CCH-P10 and FLH-P10 antisera, exhibited cross-reactivity with murine and human melanoma cells, like anti-CCH and anti-FLH sera suggesting a cross-reaction of CCH and FLH glycosylations with carbohydrate epitopes on the tumor cell surfaces, similar to the KLH antisera. When mice were primed with each hemocyanin-P10 and challenged with melanoma cells, better antitumor effects were observed for FLH-P10 than for CCH-P10 and, as for KLH-P10, irrespective of conjugation. These data demonstrate that CCH and FLH are useful carriers of carbohydrate mimotopes; however, the best antitumor activity of FLH preparations, indicate that is a suitable candidate for further cancer vaccines research.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Palacios M,Tampe R,Del Campo M,Zhong TY,López MN,Salazar-Onfray F,Becker MIdoi
10.1016/j.ejmech.2018.02.082subject
Has Abstractpub_date
2018-04-25 00:00:00pages
74-86eissn
0223-5234issn
1768-3254pii
S0223-5234(18)30225-3journal_volume
150pub_type
杂志文章abstract::A series of novel 2-amino-4-(4-methylpiperazin-1-yl)-1,3,5-triazine derivatives with different aryl substituents in the 6-position was designed, synthesized and evaluated for histamine H4 receptor (H4R) affinity in Sf9 cells expressing human H4R co-expressed with G-protein subunits. Triazine derivative 8 with a 6-(p-c...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.032
更新日期:2014-08-18 00:00:00
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
doi:10.1016/j.ejmech.2017.11.048
更新日期:2018-01-01 00:00:00
abstract::Some new substituted thienopyrimidine derivatives comprising thioxo, thioalkyl and pyrazolyl derivatives as well as fused thienotriazolopyrimidine and thienopyrimidinotriazine ring systems were prepared from 3-benzyl-2-hydrazino-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide 4. The designed compounds ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.07.007
更新日期:2012-09-01 00:00:00
abstract::We report herein the synthesis of 5-substituted [1]pyrindine derivatives and the evaluation of their antiproliferative properties on HeLa cells, a cervical carcinoma tumor cell line, and on the melanoma A2058 cell line. The most efficient compounds display cytotoxicity against tumor cells in the micromolar range but h...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.11.028
更新日期:2010-03-01 00:00:00
abstract::Current healthcare has significantly increased the average life expectancy, leading to a consequently greater incidence of age-related diseases, such as Alzheimer's disease. Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simulta...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.12.003
更新日期:2019-02-01 00:00:00
abstract::A series of novel indole-chalcone fibrates were synthesized and their hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our results...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.04.085
更新日期:2014-06-23 00:00:00
abstract::A new series of high affinity ligands and antagonists for the α1D-adrenergic receptor (AR) has been discovered. New molecules present a [1]benzothieno[3,2-d]pyrimidin-2,4(1H,3H)-dione or a [1]benzothieno[3,2-d]pyrimidin-4(3H)-one scaffold and bear a 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl moiety in the 3-position a...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.057
更新日期:2014-08-18 00:00:00
abstract::Hyaluronic acid (HA) is a mucopolysaccharide acid composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. Based on numerous characteristics such as viscoelastic properties, water-binding ability, biocompatibility and non-immunogenicity, HA has been approved by FDA for biological and m...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2014.08.067
更新日期:2014-10-30 00:00:00
abstract::This work describes the synthesis and the biological evaluation of novel benzylidenephenylpyrrolizinones as potential antioxidant, metal chelating or amyloid β (βA) aggregation inhibitors. Some derivatives exhibited interesting results in regard to several of the performed evaluations and appear as valuable Multi-Targ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.03.023
更新日期:2016-05-23 00:00:00
abstract::The syntheses of the unprotected neutral closo-carboranyl-C-deoxyriboses, starting from anomeric mixture of 1-ethynyldeoxyriboses, and their corresponding open-cage nido-derivatives have been described. The structures of both the α- and β-anomers were confirmed by single-crystal X-ray diffraction. While limited water ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.005
更新日期:2014-08-18 00:00:00
abstract::Shikonin exhibits powerful anticancer activities for various cancer cells, but its poor solubility and strong toxicity hinder its development as clinical anticancer agent. We previously confirmed that shikonin and its derivatives can disturb mitosis through targeting tubulin. In this study, α-lipoic acid, the naturall...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.12.019
更新日期:2018-01-20 00:00:00
abstract::Mono- and diacylated derivatives of galactopyranosyl amines were obtained from d-galactose, via aminated intermediates prepared by reaction of 6-deoxy-6-iodo-1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose with 1,3-propanediamine, 1,2-ethanediamine or ethanolamine. Monoacylated derivatives displayed antitubercular...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2007.01.009
更新日期:2007-08-01 00:00:00
abstract::Many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. Furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifunga...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.02.037
更新日期:2012-05-01 00:00:00
abstract::New promising unsymmetrical bisacridine derivatives (UAs), have been developed. Three groups including 36 compounds were synthesized by the condensation of 4-nitro or 4-methylacridinone, imidazoacridinone and triazoloacridinone derivatives with 1-nitroacridine compounds linked with an aminoalkyl chain. Cytotoxicity sc...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2020.112599
更新日期:2020-10-15 00:00:00
abstract::A series of novel 6-chloro-4-(2-chlorophenyl)-3-(2-hydroxyethyl) quinolin-2(1H)-one derivatives were synthesized and evaluated for anti-hepatitis B virus (anti-HBV) activities in vitro to explore their structure-activity relationships (SARs). Most of the synthesized compounds possessed potent anti-HBV activity, of whi...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.11.019
更新日期:2011-01-01 00:00:00
abstract::There is a growing interest in the cancer cell growth inhibitory effects of organotin (IV) compounds and, accordingly, a new series of dimethyl-, di-(n-butyl)-, diphenyl- and chloro-phenyl tin(IV) complexes with a Schiff base core were prepared. Their binding to DNA was assessed by UV thermal denaturation showing no i...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.07.047
更新日期:2019-11-01 00:00:00
abstract::Microtubule is one of the important targets for cancer treatment. A novel class of diaryl substituted imidazo[4,5-c]pyridin-2-ones and imidazo[4,5-c]pyridines were designed based on combination principles by merging the structures of β-lactams and purine-type compounds known as tubulin polymerization inhibitor and kat...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.05.072
更新日期:2019-09-15 00:00:00
abstract::Estrogens are steroid hormones playing critical roles in several physiological processes, which bind the estrogen receptors ERalpha and ERbeta. Aim of this work is to analyze, by different docking experiments, the behavior of a set of compounds, mimicking estrogens activity, in order to understand the relationship bet...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2004.02.014
更新日期:2004-07-01 00:00:00
abstract::A series of twenty seven oxa/azaspiro[4,5]trienone derivatives were synthesized and their anticancer properties have been explored. GI50 values of all these compounds were evaluated against four types of human cancer cell lines, i.e. MCF-7 (breast), DU-145 (prostate), A549 (lung) and HepG2 (liver). Five compounds of t...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.06.050
更新日期:2015-08-28 00:00:00
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
doi:10.1016/j.ejmech.2013.03.066
更新日期:2013-06-01 00:00:00
abstract::Two new series of quinoline incorporated benzimidazole derivatives (4a-i and 8a-f) were synthesized from substituted aniline and isatin through multi-step reaction. 6-substituted-4-carboxyquinolines (3a,b and 7) were synthesized by multi component one pot reactions (via Doebner reaction and Pfitzinger reaction respect...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.05.027
更新日期:2012-08-01 00:00:00
abstract::An efficient route without metal catalyst has been developed for synthesis of 4-biphenylamino-5-halo-2(5H)-furanones. The antitumor activities against various tumor cells of all the compounds have been evaluated by MTT assay. Among them, the compound 3j exhibits significant inhibitory activity against MCF-7 human brea...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.08.005
更新日期:2017-10-20 00:00:00
abstract::Chagas disease is a neglected tropical disease (NTD) caused by the protozoan parasite Trypanosoma cruzi and is primarily transmitted to humans by the feces of infected Triatominae insects during their blood meal. The disease affects 6-8 million people, mostly in Latin America countries, and kills more people in the re...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2018.11.062
更新日期:2019-02-01 00:00:00
abstract::Thirty new 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizur...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.01.009
更新日期:2011-04-01 00:00:00
abstract::Facing the continuously urgent demands for novel antimicrobial agents since the growing emergence of bacterial resistance, a series of new ultra-short lipopeptides, composed of tryptophan and arginine and fatty acids, were de novo designed and synthesized in this study. Most of the new lipopeptides exhibited preferabl...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2020.113138
更新日期:2020-12-29 00:00:00
abstract::Peripheral benzodiazepine receptor (PBR) is associated with neuroinflammation and tumor progression. [(11)C]DAA1106 and [(18)F]FEDAA1106 are two promising radioligands for positron emission tomography (PET) imaging of PBR. This study was designed to develop a new radiolabeled analog of [(11)C]DAA1106 and [(18)F]FEDAA1...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.08.001
更新日期:2009-06-01 00:00:00
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
doi:10.1016/j.ejmech.2020.112085
更新日期:2020-03-15 00:00:00
abstract::Three new Amaryllidaceae alkaloids, named zephycandidines I-III (1-3), were isolated from Zephyranthes candida. The structures of 1-3 were elucidated by spectroscopic analyses including HRESIMS, 1H NMR, 13C NMR, DEPT, HSQC, 1H-1H COSY, HMBC, ROESY, and electronic circular dichroism (ECD), as well as ECD calculation. T...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.10.057
更新日期:2017-02-15 00:00:00
abstract::Fms-like tyrosine kinase 3 (FLT3) is a well-known and important target for the treatment of acute myeloid leukemia (AML). A series of thieno[2,3-d]pyrimidine derivatives from a modification at the 6-position were synthesized to identify effective FLT3 inhibitors. Although compounds 1 and 2 emerged as promising FLT3 in...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.05.022
更新日期:2016-09-14 00:00:00
abstract::PI3K/Akt/mTOR signaling pathway plays an important role in cancer cell growth and survival. In this study, a new class of molecules with skeleton of 4-phenyl-2H-benzo[b] [1,4]oxazin-3(4H)-one were designed and synthesized targeting this pathway. Bioassays showed that, among all the molecules, 8d-1 was a pan-class I PI...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.06.021
更新日期:2019-09-15 00:00:00