ABSTRACT
Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Aspartic Acid Endopeptidases/antagonists & inhibitors , Drug Design , Imidazolidines/chemical synthesis , Imidazolidines/pharmacology , Piperazines/chemical synthesis , Piperazines/pharmacology , Animals , Crystallography, X-Ray , Disease Models, Animal , Humans , Imidazolidines/chemistry , Mice , Mice, Transgenic , Models, Molecular , Molecular Conformation , Molecular Structure , Piperazines/chemistry , Structure-Activity RelationshipABSTRACT
Bioassay-directed fractionation led to the isolation of 14 compounds, six of which possess antimalarial activity, from the dried leaves and stems of Rhaphidophora decursiva. Polysyphorin (1) and rhaphidecurperoxin (6) showed strong activities against Plasmodium falciparum. Rhaphidecursinol A (2), rhaphidecursinol B (3), grandisin (4), and epigrandisin (5) were less active against the same organism. Among the isolates, rhaphidecursinol A (2) and rhaphidecursinol B (3) were determined to be new neolignans, and rhaphidecurperoxin (6) is a new benzoperoxide. Known compounds isolated include polysyphorin (1), grandisin (4), epigrandisin (5), (+)-medioresinol, (-)-pinoresinol, (-)-syringaresinol, (+)-glaberide I, (+)-dehydrovomifoliol, (-)-liliolide, (-)-hydroxydihydrobovolide, and N-butylbenzamide, of which compound 1 appears worthy of further evaluation as an antimalarial agent. Structure elucidation and identification were accomplished by spectroscopic means including 1D and 2D NMR analyses.
Subject(s)
Antimalarials/chemistry , Antimalarials/isolation & purification , Plants, Medicinal/chemistry , Animals , Antimalarials/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation , Plant Leaves/chemistry , Plant Stems/chemistry , Plasmodium falciparum/drug effects , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , Tumor Cells, Cultured , VietnamABSTRACT
The pregnane steroid, (E)-aglawone, along with four known triterpenes, and a known sterol mixture were isolated from the bark of Aglaia lawii (Wight) Saldanha ex Ramamoorty (Meliaceae). The structural determination/identification was accomplished by a combination of 1D- and 2D-NMR spectroscopic techniques. The relative stereochemistry of the known triterpene, 20S,24S-epoxydammarane-3alpha,25-diol acetate, was also unequivocally determined for the first time by X-ray crystallography. The isolates were not active against various human cancer cell lines.
Subject(s)
Phytosterols/chemistry , Plants, Medicinal/chemistry , Pregnanes/chemistry , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Molecular Structure , Phytosterols/isolation & purification , Plant Stems/chemistry , Pregnanes/isolation & purificationABSTRACT
To investigate the distribution of Gnathostoma spp in Ho Chi Minh City (HCM city), 1,081 eels were purchased from a local market twice a month from March 1998 to February 1999. Infective larvae of Gnathostoma spp detected from the flesh and liver of eels by the press preparation technique were examined and identified. Three hundred and fifty advanced third-stage larvae were recovered from liver, none from the flesh. The average rate of infection was 0.11; a high rate of infection was found from August to November and a low rate of infection from February to May. The average number of larvae/eel was 2.9; the greatest number of larvae/eel was in January whereas the lowest was in March and April. There was a marked decrease in both prevalence and intensity of infection from February to May, followed by a rise from June. The finding suggests that in HCM city, the infection rate abruptly decreases soon after the end of the rainy season and starts to rise when the rain comes and reaches its peak at the end of the rainy season. All recovered larvae were identified as G. spinigerum.
