Asunto(s)
Cordia/química , Naftoquinonas/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Brasil , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química , Raíces de Plantas/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Saint Peter and Saint Paul's Archipelago is a collection of 15 islets and rocks remotely located in the equatorial Atlantic Ocean. In this particular site, the present project intended to assess the biodiversity and biotechnological potential of bacteria from the actinomycete group. This study presents the first results of this assessment. From 21 sediment samples, 268 strains were isolated and codified as BRA followed by three numbers. Of those, 94 strains were grown in liquid media and submitted to chemical extractions with AcOEt (A), BuOH (B), and MeOH (M). A total of 224 extracts were screened for their cytotoxic activity and 41 were significantly active against HCT-116 cancer cells. The obtained IC50 values ranged from 0.04 to 31.55 µg/ml. The HR-LC/MS dereplication analysis of the active extracts showed the occurrence of several known anticancer compounds. Individual compounds, identified using HR-MS combined with analysis of the AntiMarin database, included saliniketals A and B, piericidins A and C and glucopiericidin A, staurosporine, N-methylstaurosporine, hydroxydimethyl-staurosporine and N-carbamoylstaurosporine, salinisporamycin A, and rifamycins S and B. BRA-199, identified as Streptomyces sp., was submitted to bioassay-guided fractionation, leading to isolation of the bioactive piericidins A and C, glucopiericidin, and three known diketopiperazines, cyclo(l-Phe-trans-4-OH-l-Pro), cyclo(l-Phe-l-Pro), and cyclo(l-Trp-l-Pro).
Asunto(s)
Actinobacteria/química , Actinobacteria/aislamiento & purificación , Antineoplásicos Fitogénicos/análisis , Antineoplásicos Fitogénicos/farmacología , Sedimentos Geológicos/microbiología , Antineoplásicos Fitogénicos/química , Brasil , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Conformación Molecular , Relación Estructura-ActividadRESUMEN
Three new plakortides, 7,8-dihydroplakortide E (1), 2, and 10, along with known natural products 3, 4, spongosoritin A (5), 6-8, and plakortide P (9), were isolated from Brazilian specimens of Plakortis angulospiculatus. Compounds 2, 3, 5, and 7-9 displayed cytotoxic activities with IC50 values ranging from 0.2 to 10 µM. Compounds that contained a dihydrofuran ring were generally less active and displayed time dependence in their activity. The activities of compounds 2 and 7-9, carboxylic acids bearing a common six-membered endoperoxide, were higher overall than for compounds 3 and 5. The modes underlying the cytotoxic actions of plakortides 2, 3, 5, 7, and 9 were further investigated using HCT-116 cells. While dihydrofurans 3 and 5 induce a G0/G1 arrest, six-membered peroxides 2, 7, and 9 delivered a G2/M arrest and an accumulation of mitotic figures, indicating a distinctly different antimitotic response. Confocal analysis indicated that microtubules were not altered after treatment with 2, 7, or 9, therein suggesting that the mitotic arrest may be unrelated to cytoskeletal targets. Overall, we find that two related classes of natural products obtained from the same extract offer cytostatic activity, yet they do so through discrete pathways.