Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Org Chem ; 89(9): 6074-6084, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38626391

RESUMO

A PPh3Au[B(C6F5)4]-catalyzed reaction of enynals and alkenes for the construction of binaphthyl derivatives was described. This transformation was achieved through o-Quinodimethane (o-QDM) intermediate's extended conjugated addition process. The reaction has the advantages of wide substrate scopes, mild reaction conditions, high efficiency, and good scalability.

2.
J Am Chem Soc ; 146(12): 8547-8556, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38498689

RESUMO

Photocatalysis has found increasing applications in biological systems, for example, in localized prodrug activation; however, high-energy light is usually required without giving sufficient efficiency and target selectivity. In this work, we report that ion pairing between photocatalysts and prodrugs can significantly improve the photoactivation efficiency and enable tumor-targeted activation by red light. This is exemplified by a gold-based prodrug (1d) functionalized with a morpholine moiety. Such a modification causes 1d to hydrolyze in aqueous solution, forming a cationic species that tightly interacts with anionic photosensitizers including Eosin Y (EY) and Rose Bengal (RB), along with a significant bathochromic shift of absorption tailing to the far-red region. As a result, a high photoactivation efficiency of 1d by EY or RB under low-energy light was found, leading to an effective release of active gold species in living cells, as monitored by a gold-specific biosensor (GolS-mCherry). Importantly, the morpholine moiety, with pKa ∼6.9, in 1d brings in a highly pH-sensitive and preferential ionic interaction under a slightly acidic condition over the normal physiological pH, enabling tumor-targeted prodrug activation by red light irradiation in vitro and in vivo. Since a similar absorption change was found in other morpholine/amine-containing clinic drugs, photocages, and precursors of reactive labeling intermediates, it is believed that the ion-pairing strategy could be extended for targeted activation of different prodrugs and for mapping of an acidic microenvironment by low-energy light.


Assuntos
Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/química , Luz Vermelha , Morfolinas , Microambiente Tumoral
3.
Org Lett ; 25(7): 1192-1197, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36779678

RESUMO

A cost-effective, highly regioselective and metal-free version for the synthesis of indolizine derivatives by means of Tf2O-mediated cascade reaction of pyridyl-enaminones and thiophenols/thioalcohols under mild reaction conditions has been reported. Diverse electron-rich indolizine derivatives could be obtained in up to 94% yield via the selective 1,4-addition of vinyl iminium triflate tandem cyclization/aromatization, which allowed the simultaneous construction of C-N and C-S/and one example of C-Se bonds.

4.
J Inorg Biochem ; 239: 112083, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36508972

RESUMO

Herein, three pairs of cationic cyclometallated palladium (II) complexes with different types of C^N ligands, which is non-phosphorescent in aqueous solution, interestingly, they can be utilized as turn-on blue phosphorescent probes selectively for ClO-, HSO3- and CO32-, and turn-on green phosphorescent probe for HSO3- in aqueous solution. These different phosphorescent turn-on responses of Pd(II) complexes could be attributed to the degree of coordination and electrostatic interaction between them with specific anion. It suggests that the selectivity towards specific anion of these cyclometallated Pd(II) complexes can be further improved by rationally tuning the structure and enhancing aromaticity of C^N ligand. Our study reveals that these specific species of anions can effectively induce self-assembly of Pd(II) compounds with different C^N ligand based on PdPd interaction, the aggregation and morphology of palladium complex with anion in aqueous media was also investigated by various means of 1H NMR, UV/Vis, fluorescence spectra, and dynamic light scattering (DLS) analysis. Moreover, transmission electron microscopy (TEM) reveals that nanowires with increased length of diameters of Pd complexes can form in aqueous solution in presence of anions with different high concentration. Furthermore, the cellular uptake and location of Pd2a was also investigated by confocal imaging for the first time. DFT calculation of monomer and dimer of Pd2a was also performed, which is helpful to explain the turn on phosphorescent effect during self-assembly process.


Assuntos
Paládio , Água , Paládio/química , Ligantes , Água/química , Ânions , Medições Luminescentes
5.
Angew Chem Int Ed Engl ; 61(16): e202201103, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35165986

RESUMO

Spatiotemporally controllable activation of prodrugs within tumors is highly desirable for cancer therapy to minimize toxic side effects. Herein we report that stable alkylgold(III) complexes can undergo unprecedented photo-induced ß-hydride elimination, releasing alkyl ligands and forming gold(III)-hydride intermediates that could be quickly converted into bioactive [AuIII -S] adducts; meanwhile, the remaining alkylgold(III) complexes can photo-catalytically reduce [AuIII -S] into more bioactive AuI species. Such photo-reactivities make it possible to functionalize gold complexes on the auxiliary alkyl ligands without attenuating the metal-biomacromolecule interactions. As a result, the gold(III) complexes containing glucose-functionalized alkyl ligands displayed efficient and tumor-selective uptake; notably, after one- or two-photon activation, the complexes exhibited high thioredoxin reductase (TrxR) inhibition, potent cytotoxicity, and strong antiangiogenesis and antitumor activities in vivo.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Ouro , Humanos , Ligantes , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Tiorredoxina Dissulfeto Redutase
6.
Angew Chem Int Ed Engl ; 59(27): 11046-11052, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32207866

RESUMO

The specific gold-sulfur binding interaction renders gold complexes as promising anti-cancer agents that can potentially overcome cisplatin resistance; while their unbiased binding towards non-tumoral off-target thiol-proteins has posed a big hurdle to clinical application. Herein we report that cyclometalated gold(III) complexes bearing hydride ligands are highly stable towards thiols in the dark but can efficiently dissociate the auxiliary hydride moiety and generate a gold-thiol adduct when excited with visible light. In consequence, the photo-activated gold(III) complexes potently inhibited thioredoxin reductase in association with up to >400-fold increment of photocytotoxicity (vs. dark condition) without deactivation by serum albumin and along with strong anti-angiogenesis activity in zebrafish embryos. Importantly, the gold(III)-hydride complexes could be activated by two-photon laser irradiation at the phototherapeutic window as effectively as blue-light irradiation.


Assuntos
Antineoplásicos/química , Ouro/química , Luz , Compostos de Sulfidrila/química , Animais , Linhagem Celular Tumoral , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Peixe-Zebra/embriologia
7.
Chem Commun (Camb) ; 55(87): 13066-13069, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31570904

RESUMO

A platinum(ii) complex containing an aminophosphonate ligand preferentially accumulates in the endoplamic reticulum (ER) in association with potent ER stress and reactive oxygen species generation, followed by the activation of damage-associated molecular pattern signals and immune responses. Importantly, the Pt complex exhibits potent anti-tumour activities in two independent mouse models via an immunogenic cell death pathway.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Ésteres/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Organofosfonatos/farmacologia , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos Imunológicos/química , Morte Celular/efeitos dos fármacos , Ésteres/química , Humanos , Ligantes , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Organofosfonatos/química , Compostos Organoplatínicos/química
8.
Org Lett ; 18(20): 5208-5211, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27696869

RESUMO

An efficient method for the synthesis of polysubstituted aziridines utilizing enynones and imines is described. This transformation is achieved through the reaction of imines with donor/donor carbene intermediates, which were generated in situ from the cyclization of enynones. Furthermore, the resulted aziridines were good 1,3-dipoles, which could be efficiently trapped by dipolarophiles to give five-membered heterocycles. The obvious advantages of wide substrate scopes, mild reaction conditions, and high atom efficiency make this system highly appealing for construction of polysubstituted aziridines, 2,5-dihydropyroles, and 1,2,4-triazolidines.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...