RESUMEN
The Republic of Maldives' black marine sponge Hyrtios erecta has been found to contain three cancer cell-line inhibitory pentacyclic sesterterpenes designated sesterstatins 1-3 (2-4). One of the sesterterpenes, sesterstatin 2, specifically inhibited the Gram-positive opportunist Staphylococcus aureus. All three of the P-388 lymphocytic-leukemia-active (ED50 0.46 to 4.3 micrograms/mL) sesterstatins were obtained in trace quantities (3.0 x 10-7 to 5.4 x 10-7% yields) and represent structural variations on the more usual scalarin-type porifera sesterterpenes. The structures were elucidated by highfield (500 MHz) 2D NMR techniques augmented by HRMS results.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Poríferos/química , Terpenos/aislamiento & purificación , Animales , Antibacterianos , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Bacterias/efectos de los fármacos , Secuencia de Carbohidratos , Cromatografía en Capa Delgada , Hongos/efectos de los fármacos , Leucemia P388/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Espectrofotometría Ultravioleta , Terpenos/farmacologíaRESUMEN
The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).
Asunto(s)
Antineoplásicos/química , Poríferos , Terpenos/química , Terpenos/aislamiento & purificación , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/toxicidad , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Islas del Oceano Índico , Leucemia P388 , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Relación Estructura-Actividad , Terpenos/toxicidad , Células Tumorales CultivadasRESUMEN
By means of bioassay-guided separation methods, the cancer cell growth inhibitory constituents residing in the bark, stem and leaves of the Mauritius medicinal plant Terminalia arjuna (Combretaceae) were examined. The cancer cell line active components were found to be gallic acid, ethyl gallate, and the flavone luteolin. Only gallic acid was previously known to occur in this plant. Luteolin has a well established record of inhibiting various cancer cell lines and may account for most of the rationale underlying the use of T. arjuna in traditional cancer treatments. Luteolin was also found to exhibit specific activity against the pathogenic bacterium Neisseria gonorrhoeae.