Asunto(s)
Analgésicos Opioides/química , Dolor/tratamiento farmacológico , Tramadol/química , Analgésicos Opioides/aislamiento & purificación , Fitoquímicos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Plantas Medicinales/química , Tramadol/aislamiento & purificaciónRESUMEN
We report the synthesis and in vitro antiplasmodial activity of 35 compounds, designed as analogues of the naturally occurring aurones. Several of these analogues showed submicromolar antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum (FcB1-Columbia strain) cultured on human erythrocytes. Substitution of the intracyclic oxygen in aurones by a nitrogen atom and systematic variation of the substituent at the B-ring revealed promising leads showing good activity on the CQ-resistant strain. In particular, 4,6-dimethoxy-4'-ethylazaaurone 22 showed antiplasmodial potency without noticeable toxicity. The easy synthesis of this family of compounds and the relevant antiplasmodial activity are in favor of promising candidates for further development.
Asunto(s)
Antimaláricos/química , Compuestos Aza/química , Benzofuranos/química , Indoles/química , Antimaláricos/síntesis química , Antimaláricos/farmacología , Benzofuranos/síntesis química , Benzofuranos/farmacología , Eritrocitos/parasitología , Humanos , Indoles/síntesis química , Indoles/farmacología , Plasmodium falciparum/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
We report the synthesis of 5-hydroxy-7-methoxy-2-phenyl-4-quinolones and their biological activity as antitumor agents. These molecules were initially evaluated for their ability to induce cell cycle arrest in the G2/M phase. Compounds that showed significant G2/M cell cycle arrest were tested for antiproliferative activity using both the MTT assay and the NCI in vitro 60 cell line human tumor screen. The 5-hydroxy-7-methoxy-2-phenyl-4-quinolone (3a) and 2-(3-fluorophenyl)-5-hydroxy-7-methoxy-4-quinolone (3f) were the most active in the cell cycle arrest test whereas 3f was found to be the most active in the MTT assay. In terms of structural requirements, we found that the presence of a 5-hydroxyl group, a 7-methoxy group, and an unsubstituted N1 were essential for the antimitotic activity. In accordance with the literature, a fluoro group at the 3'- or 2'-position and a methoxy or a chloro group at the 3'-position were found to be highly advantageous for both the cell cycle arrest and the antiproliferative activities.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Quinolonas/química , Quinolonas/farmacología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Fase G2/efectos de los fármacos , Humanos , Células K562 , Mitosis/efectos de los fármacos , Relación Estructura-Actividad , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismoRESUMEN
A series of 4-hydroxy-6-methoxyaurones and 4,6-dimethoxyaurones has been synthesised and tested for their binding affinity toward the nucleotide-binding domain of P-glycoprotein, an ABC (ATP-Binding Cassette) transporter which mediates the resistance of cancer cells to chemotherapy. These compounds differ from each other by the nature of the substituent on the aurone B-ring. The binding affinity seems to be linked to the nature of the substituent, as well as to the presence or the absence of a hydroxy group at position 4. The most active compounds were 4'-bromo-4-hydroxy-6-methoxyaurone and 4-hydroxy-4'-iodo-6-methoxyaurone.
