RESUMO
Argireline (Ac-EEMQRR-NH2 ), a well-known neurotransmitter peptide with a potency similar to botulinum neurotoxins, reveals a proven affinity toward Cu(II) ions. We report herein Cu(II) chelating properties of three new Argireline derivatives, namely, AN4 (Ac-EAHRR-NH2 ), AN5 (Ac-EEHQRR-NH2 ), and AN6 (Ac-EAHQRK-NH2 ). Two complementary experimental techniques, i.e., potentiometric titration (PT) and isothermal titration calorimetry (ITC), have been employed to describe the acid-base properties of the investigated peptides as well as the thermodynamic parameters of the Cu(II) complex formation. Additionally, based on density functional theory (DFT) calculations, we propose the most likely structures of the resulting Cu-peptide complexes. Finally, the cytotoxicity of the free peptides and the corresponding Cu(II) complexes was estimated in human skin cells for their possible future cosmetic application. The biological results were subsequently compared with free Argireline, its Cu(II)-complexes, and the previously studied AN2 derivative (EAHQRR).
Assuntos
Complexos de Coordenação , Cobre , Humanos , Cobre/química , Peptídeos/farmacologia , Peptídeos/química , Oligopeptídeos/química , Íons , Complexos de Coordenação/farmacologia , Complexos de Coordenação/químicaRESUMO
Seven oleanane-type glycosides were extracted and isolated by various chromatographic methods from the roots of Weigela x "Bristol Ruby" (1-7), six previously undescribed (1-6) and a known one (7). Their structures were assigned by spectroscopic analysis mainly 2D NMR and mass spectrometry (ESIMS). Selected triterpenoid glycosides (1-3, 6, 7) displayed a good cytotoxic activity against a mouse colon cancer cell line CT26.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Caprifoliaceae/química , Glicosídeos/farmacologia , Ácido Oleanólico/análogos & derivados , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Camundongos , Estrutura Molecular , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Three triterpene glycosides were isolated from the roots of Weigela florida "rumba" (Bunge) A. DC.: two previously undescribed 3-O-ß-d-xylopyranosyl-(1â2)-[ß-d-xylopyranosyl-(1â4)]-ß-d-xylopyranosyl-(1â4)-ß-d-xylopyranosyl-(1â3)-α-L-rhamnopyranosyl-(1â2)-α-l-arabinopyranosyloleanolic acid (1) and 3-O-ß-d-xylopyranosyl-(1â2)-[ß-d-glucopyranosyl-(1â4)]-ß-d-xylopyranosyl-(1â4)-ß-d-xylopyranosyl-(1â3)-α-l-rhamnopyranosyl-(1â2)-α-L-arabinopyranosyloleanolic acid (2), and one isolated for the first time from a natural source 3-O-ß-d-xylopyranosyl-(1â3)-α-l-rhamnopyranosyl-(1â2)-α-l-arabinopyranosyloleanolic acid (3). Their structures were elucidated mainly by 2D NMR spectroscopic analysis (COSY, TOCSY, NOESY, HSQC, HMBC) and mass spectrometry. Compounds 2 and 3 were further evaluated as antigens in enzyme-linked immunosorbent assay (ELISA) to recognize IgM antibodies in multiple sclerosis (MS) patients' sera.
Assuntos
Caprifoliaceae/química , Glicosídeos/isolamento & purificação , Ácido Oleanólico/análogos & derivados , Raízes de Plantas/química , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina M/química , Estrutura Molecular , Esclerose Múltipla/sangue , Ácido Oleanólico/isolamento & purificaçãoAssuntos
Ácido Oleanólico/análogos & derivados , Raízes de Plantas/química , Saponinas/química , Wisteria/química , Cromatografia Gasosa , Hidrólise , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Ácido Oleanólico/química , Extratos Vegetais/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The Trp-rich motif (TrpM) of the transmembrane glycoprotein (TM) of lentiviruses is an attractive domain on which to design new potential cell entry peptide inhibitors. We recently demonstrated that an octapeptide reproducing the TrpM of feline immunodeficiency virus (FIV), designated C8, broadly inhibited this virus in vitro and that the retroinverso analogue of this peptide (riC8) was almost as inhibitory and exhibited features suggestive of a much increased stability. Here, we demonstrated that riC8 is indeed highly stable, maintaining its concentration unchanged for at least 24 h in cat serum in vitro. Furthermore, once inoculated into cats, riC8 produced no major acute toxic effects and exhibited satisfactory pharmacokinetic properties. Finally, we report the results of a short-term monotherapy experiment in chronically FIV-infected cats showing that riC8 is well tolerated and also has substantial antiviral activity in vivo. In particular, the mean viral load of riC8-treated animals declined progressively with increasing time of treatment, whereas that of control animals given C8 or solvent alone did not. These results provide the first evidence that clinically useful inhibition of virus replication with a small peptide derived from a functional domain of the TM of a lentivirus can be achieved in vivo.