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1.
ACS Infect Dis ; 9(7): 1334-1345, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37307287

RESUMO

Six new ether phospholipid analogues encompassing constituents from cashew nut shell liquid as the lipid portion were synthesized in an effort to valorize byproducts of the cashew industry toward the generation of potent compounds against Chagas disease. Anacardic acids, cardanols, and cardols were used as the lipid portions and choline as the polar headgroup. The compounds were evaluated for their in vitro antiparasitic activity against different developmental stages of Trypanosoma cruzi. Compounds 16 and 17 were found to be the most potent against T. cruzi epimastigotes, trypomastigotes, and intracellular amastigotes exhibiting selectivity indices against the latter 32-fold and 7-fold higher than current drug benznidazole, respectively. Hence, four out of six analogues can be considered as hit-compounds toward the sustainable development of new treatments for Chagas disease, based on inexpensive agro-waste material.


Assuntos
Anacardium , Doença de Chagas , Tripanossomicidas , Desenvolvimento Sustentável , Nozes , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Lipídeos
2.
Eur J Med Chem ; 122: 601-610, 2016 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-27448917

RESUMO

Arylpiperazines 2-11 were synthesized, and their biological profiles at α1-adrenergic receptors (α1-ARs) assessed by binding assays in CHO cells expressing human cloned subtypes and by functional experiments in isolated rat vas deferens (α1A), spleen (α1B), and aorta (α1D). Modifications at the 1,3-benzodioxole and phenyl phamacophoric units resulted in the identification of a number of potent compounds (moderately selective with respect to the α1b-AR), in binding experiments. Notably, compound 7 (LDT451) showed a subnanomolar pKi of 9.41 towards α1a-AR. An encouragingly lower α1B-potency was a general trend for all the series of compounds, which showed α1A/D over α1B selectivity in functional assays. If adequately optimized, such peculiar selectivity could have relevance for a potential LUTS/BPH therapeutic application.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/síntese química , Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Desenho de Fármacos , Piperazinas/síntese química , Piperazinas/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/química , Antagonistas de Receptores Adrenérgicos alfa 1/metabolismo , Animais , Células CHO , Linhagem Celular Tumoral , Técnicas de Química Sintética , Clonagem Molecular , Cricetinae , Cricetulus , Humanos , Masculino , Simulação de Acoplamento Molecular , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Piperazinas/química , Piperazinas/metabolismo , Conformação Proteica , Ratos , Receptores Adrenérgicos alfa 1/química , Receptores Adrenérgicos alfa 1/genética , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
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