RESUMEN
Chromatographic separation of extracts from the fungal biomass of a plant pathogenic fungus, Myrothecium roridum, yielded 8 trichothecene toxins including 6 type D trichothecenes (1: -6: ) and 2 type A trichothecenes (7: -8: ). 6',12'-Epoxymyrotoxin A (1: ) and 7'-hydroxymytoxin B (2: ) were new macrocyclic trichothecenes, while the other trichothecenes were identified as myrotoxin B (3: ), myrotoxin D hydrate (4: ), 2',3'-epoxymyrothecine A (5: ), miotoxin A (6: ), and 2 trichothecenes lacking the macrocyclic lactone system, roridin L-2 (7: ) and trichoverritone (8: ). The structures of these mycotoxins were characterized using spectroscopic methods. The absolute configurations of 1: and 2: were determined by NOESY and a comparison of their experimental and calculated ECD spectra. Most of these mycotoxins (1: -4: and 6: ) exhibited highly potent antimalarial activity against Plasmodium falciparum. They also showed strong cytotoxicity towards KB and NCI-H187 cell lines (IC50 0.60â-â112.28 nM), as well as the Vero cell line (IC50 1.50â-â46.51 nM).
Asunto(s)
Antimaláricos/farmacología , Antineoplásicos/farmacología , Hypocreales/química , Micotoxinas/farmacología , Tricotecenos/química , Animales , Antimaláricos/química , Antineoplásicos/química , Línea Celular Tumoral , Chlorocebus aethiops , Evaluación Preclínica de Medicamentos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Micotoxinas/química , Plasmodium falciparum/efectos de los fármacos , Relación Estructura-Actividad , Tricotecenos/farmacología , Células VeroRESUMEN
Chromatographic separation of fruits and flowers of the Thai medicinal plant, Miliusa velutina, resulted in the isolation of five new rare homogentisic acid derivatives, miliusanal (1) and miliusanones A-D (2-5), together with fifteen known secondary metabolites (6-20). Their structures were determined through the use of extensive spectroscopic data. The absolute configurations of homogentisic acid derivatives 2-7 were identified using NOESY data and a comparison of experimental and calculated ECD spectral data. Compounds 2, 3, 6, and 7 showed antimalarial activity with IC50 values in the range of 3.3-5.2⯵g/mL. Compound 6 also showed activity against Mycobacterium tuberculosis with an MIC value of 50⯵g/mL. Compounds 1-3, 6 and 7 exhibited cytotoxicity againt KB, MCF-7, NCI-H187 and Vero cell lines with IC50 values in the range of 5.8-40.4⯵g/mL. In addition, compounds 1, 2 and 6 showed moderate antibacterial activities against three Gram-positive bacteria (Bacillus cereus, Staphylococcus aureus, and Methicillin resistant S. aureus) with MICs in the range of 32-64⯵g/mL.