RESUMO
A potent antiplasmodial polycyclic xanthone, MDN-0185 (1), was isolated from an unidentified species of the genus Micromonospora. The planar structure of 1 was established as a seven-ring polycyclic xanthone with partial structures very similar to two known natural products, namely, xantholipin and Sch 54445. Using ROESY correlations, the relative stereochemistry of the two independent stereoclusters of compound 1 could be determined. Mosher analysis and comparison of the specific rotation of compound 1 with that of xantholipin allowed the determination of its absolute configuration. Compound 1 exhibited an IC50 of 9 nM against Plasmodium falciparum 3D7 parasites.
Assuntos
Antimaláricos/isolamento & purificação , Micromonospora/química , Plasmodium falciparum/efeitos dos fármacos , Compostos Policíclicos/isolamento & purificação , Xantonas/isolamento & purificação , Antimaláricos/química , Antimaláricos/farmacologia , Estrutura Molecular , Compostos Policíclicos/química , Compostos Policíclicos/farmacologia , Xantonas/química , Xantonas/farmacologiaRESUMO
A new napyradiomycin, MDN-0170 (1), was isolated from the culture broth of the marine-derived actinomycete strain CA-271078, together with three known related compounds identified as 4-dehydro-4a-dechloronapyradiomycin A1 (2), napyradiomycin A1 (3) and 3-chloro-6,8-dihydroxy-8-α-lapachone (4). The structure of the new compound was determined using a combination of spectroscopic techniques, including 1D and 2D NMR and electrospray-time of flight mass spectrometry (ESI-TOF MS). The relative configuration of compound 1, which contains two independent stereoclusters, has been established by molecular modelling in combination with nOe and coupling constant analyses. Biosynthetic arguments also allowed us to propose its absolute stereochemistry. The antimicrobial properties of the compounds isolated were evaluated against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Aspergillus fumigatus, and Candida albicans. The potent bioactivity previously reported for compounds 2 and 3 against methicillin-sensitive S. aureus has been extended to methicillin-resistant strains in this report.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Naftoquinonas/química , Naftoquinonas/farmacologia , Streptomyces/química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Meios de Cultura , Escherichia coli/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Conformação Molecular , Espectrometria de Massas por Ionização por Electrospray , Streptomyces/classificação , Streptomyces/isolamento & purificaçãoRESUMO
Bioassay-guided compound isolation led to the discovery of two new scalarane sesterterpenes (1 and 2) and two new triterpenes (3 and 4) from two mushroom species, Pleurotus ostreatus (edible) and Scleroderma areolatum, collected from Ghana. Their structures, including absolute stereochemistry, were established by spectroscopic methods, particularly (+)-ESI-TOF mass spectrometry and 1D and 2D NMR. The four compounds exhibited IC50 values of 1.65-7.63⯵M against Plasmodium falciparum 3D7 and 5.04-13.65⯵M against Trypanosoma cruzi Tulahuen C4 parasites and were also non-cytotoxic against HepG2 tumoral human liver cells. This is the first report describing the isolation of sesterterpenes belonging to the scalarane structural class from a terrestrial source.