RESUMEN
The search for active microorganisms for the biotransformation of guttiferone A (1) and C (6) has been successfully undertaken from a collection of endophytic fungi of Symphonia globulifera. Of the twenty-five isolates obtained from the leaves, three are active and have been identified as Bipolaris cactivora. The products obtained are the result of xanthone cyclisation with the formation of two regioisomers among four possible and corresponding to 1,16-oxy-guttiferone and 3,16-oxy-guttiferone. The biotransformation conditions were studied. Interestingly, both oxy-guttiferones A are present in the plant, and the ratio of 3,16-oxy-guttiferone to 1,16-oxy-guttiferone is 4 : 1, very close to that observed by biotransformation (3.8 : 1). These results are consistent with the involvement of endophytes in their formation pathway from guttiferone A, in planta. Finally, biotransformation made it possible to obtain and describe for the first time oxy-guttiferones C.
Asunto(s)
Benzofenonas/metabolismo , Bipolaris/metabolismo , Endófitos/metabolismo , Malpighiales/microbiología , Biotransformación , Malpighiales/química , Hojas de la Planta/química , Hojas de la Planta/microbiologíaRESUMEN
Drug screening for antimalarials uses heme biocrystallization inhibition methods as an alternative to parasite cultures, but they involve complex processes and cannot detect artemisinin-like molecules. The described method detects heme-binding compounds by mass spectrometry, using dissociation of the drug-heme adducts to evaluate putative antiplasmodial activity. Applied to a chemical library, it showed a good hit-to-lead ratio and is an efficient early stage screening for complex mixtures like natural extracts.
Asunto(s)
Antimaláricos/análisis , Antimaláricos/farmacología , Descubrimiento de Drogas/métodos , Hemo/química , Espectrometría de Masas/métodos , Antimaláricos/química , Artemisininas/análisis , Artemisininas/química , Artemisininas/farmacologíaRESUMEN
A series of 3'-aminoflavones 5,6,7,8-tetra- or 5,7-dioxygenated on the A-ring was synthesized from tangeretin or naringin, two natural Citrus flavonoids. These flavones were evaluated for antiproliferative activity, activation of apoptosis, and inhibition of tubulin assembly. The most antiproliferative flavones exhibit a common 5-hydroxy-6,7,8-trimethoxy substitution pattern on the A-ring.
Asunto(s)
Antineoplásicos/síntesis química , Flavonas/síntesis química , Antineoplásicos/química , Antineoplásicos/toxicidad , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Flavanonas/química , Flavonas/química , Flavonas/toxicidad , HumanosRESUMEN
A series of chalcones polyoxygenated on the ring A (with pentamethoxy or 2'-hydroxy-3',4',5',6'-tetramethoxy substitution patterns) was synthesized from tangeretin, a natural Citrus flavonoid. These chalcones were evaluated for their antiproliferative, activation of apoptosis, inhibition of tubulin assembly and antileishmanial activities. Comparison with the reference analogous 3',4',5'-trimethoxylated chalcones showed that such peroxygenated substitution patterns on the ring A were less beneficial to these activities.
Asunto(s)
Chalconas/síntesis química , Chalconas/farmacología , Flavonas/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Antiprotozoarios/síntesis química , Antiprotozoarios/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Humanos , Leishmania/efectos de los fármacos , Extractos Vegetales , Relación Estructura-Actividad , Tubulina (Proteína)/efectos de los fármacosRESUMEN
Regioselective O-demethylation of the flavones tangeretin (1) and 3-hydroxytangeretin (6) into their 4'-O-demethylated metabolites was performed by using an Aspergillus niger strain. This method serves as a straightforward alternative to multistep synthesis or semisynthesis. The microbial approach is complementary to the chemical procedure, which furnishes a 5-O-demethylated product. P450 inhibitors prevented the biotransformation of tangeretin (1). These results suggest that a P450 oxidation system might be involved in this O-demethylation and demonstrate a consequent similarity in both microbial and mammalian metabolism of polymethoxylated flavones.
Asunto(s)
Aspergillus niger/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Flavonas/metabolismo , Aspergillus niger/química , Biotransformación , Inhibidores Enzimáticos del Citocromo P-450 , Flavonas/química , Flavonas/aislamiento & purificación , Estructura MolecularRESUMEN
Semisynthesis of linarin and acacetin from the Citrus flavonoid diosmin was performed via, as first intermediate, the 3'-O-phenyltetrazolyl ether of diosmin. This paper relates also a semisynthetic access to 6-iodoapigenin derivatives, which are key compounds in the synthesis of some biflavonoids such as robustaflavone.