RESUMO
Psoralen (1a) was found to be a specific and potent antimicrobial lead against Helicobacter pylori (H. pylori) from a traditional Chinese medicine (TCM) in the bioassay directed isolation. A series of structurally diverse analogues of 1a were thus designed and synthesized to improve the antimicrobial potency, some of which showed more potent activities than the lead compound (1a) against H. pylori. Among them, compound 25a is 16-fold stronger (MIC = 0.39 µg/mL) than 1a (MIC = 6.25 µg/mL), and is even potent than the positive control metronidazole (MIC = 0.50 µg/mL). The in vitro antimicrobial activities against H. pylori of these structurally diverse analogues based on the scaffold of 1a have also led to an outline of structure-activity relationship.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Medicina Tradicional Chinesa , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-AtividadeRESUMO
[structure: see text] Chlorahololides A(1) and B(2), two highly complex sesquiterpenoid dimers, were isolated from Chloranthus holostegius. Their structures and absolute configurations were established by NMR spectroscopy, X-ray crystallography, and CD. Chlorahololides A (1) and B (2) exhibited potent and selective inhibition on the delayed rectifier (IK) K+ current, with an IC50 of 10.9 and 18.6 microM, respectively.
Assuntos
Magnoliopsida/química , Bloqueadores dos Canais de Potássio/química , Sesquiterpenos/química , Dicroísmo Circular , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Magnoliopsida/metabolismo , Modelos Moleculares , Estrutura Molecular , Bloqueadores dos Canais de Potássio/isolamento & purificação , Bloqueadores dos Canais de Potássio/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacologia , EstereoisomerismoRESUMO
[structure: see text] Two novel tetranortriterpenoids, turrapubesins A (1) and B (2), representing the first examples of halogenated and maleimide-bearing limonoids, were isolated from the twigs and leaves of Turraea pubescens. The structures of 1 and 2 were elucidated by extensive spectroscopic analysis. Their absolute configurations were determined by X-ray crystallography of 1 and by CD analysis of a dihydrogenated derivative of 2. Turrapubesin A (1) exhibited weak cytotoxicity against the P-388 tumor cell line.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Limoninas/isolamento & purificação , Meliaceae/química , Plantas Medicinais/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Leucemia P388 , Limoninas/química , Limoninas/farmacologia , Camundongos , Estrutura Molecular , Folhas de PlantaRESUMO
Novel artemisinin derivatives bearing Mannich base group were prepared and tested for their antimalarial activity. These water-soluble artemisinin derivatives were more stable than sodium artesunate and few compounds were found to be more active against Plasmodium berghei in mice than artesunic acid by oral administration. Two most potent derivatives 17b and 17d were examined for their antimalarial activity against Plasmodium knowlesi in rhesus monkeys.
