ABSTRACT
The stereoselective synthesis of epi-thieno analogues of the phenanthroquinolizidine bioactive alkaloids (-)-Cryptopleurine and (-)-(15R)-Hydroxycryptopleurine was achieved in five steps starting from easily available enantiopure (S)-2-aminoadipic acid used as chiral pool and nitrogen atom source. During these investigations, both π-cationic cyclization of chiral N-thienylmethyl-6-oxopipecolinic acids into pure (S)-keto-lactams and theirs regioselective and diastereoselective reduction, considered as key steps of this sequence, were studied. Of particular interest, the Friedel-Crafts cyclization using (CF3CO)2O/BF3·Et2O show that near the expected keto-lactams, enamides and enamidones containing trifluoromethyl residue were isolated. A mechanism leading to the latter products with high synthetic potential was discussed.
ABSTRACT
In the course of study of epiphytic microorganisms occurring on the surface of roots of Taxus baccata L. a new strain Streptomyces sp. AC113 was isolated. According to 16S ribosomal DNA-based identification the new strain is 99% identical with Streptomyces flavidofuscus. This strain cultivated in an arginine glycerol medium produced three major metabolites identified as (-)-8-O -methyltetrangomycin (1), 8-O -methyltetrangulol (2) and 8-O -methyl-7-deoxo-7-hydroxytetrangomycin (3). The chemical structures of these angucyclines were elucidated by 1D and 2D NMR as well as by mass spectrometry. Isolated angucycline metabolites showed significant antimicrobial activity against Bacillus cereus and Listeria mocytogenes. Cytotoxic activities of compounds 1, 2 and 3 against four cell lines (B16, HT-29 and non - tumor V79, L929) were evaluated. Compound 3 was the most potent anticancer agents with IC(50) 0.054 microg/ml against cell line B16.
Subject(s)
Anthraquinones/pharmacology , Anti-Bacterial Agents/pharmacology , Streptomyces/isolation & purification , Streptomyces/metabolism , Taxus/microbiology , Anthraquinones/chemistry , Anthraquinones/isolation & purification , Anthraquinones/toxicity , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/toxicity , Bacillus cereus/drug effects , Cell Line , Culture Media/chemistry , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Humans , Inhibitory Concentration 50 , Listeria monocytogenes/drug effects , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Plant Roots/microbiology , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNAABSTRACT
Advanced glycation end products (AGEs) play a key role in the pathogenesis of diabetes and its complications, including the diabetic nephropathy. The renoprotective effects of exercise are well known; however, the mechanisms remain elusive. Here we examined whether a regular moderate exercise in obese Zucker rats (OZR), a model of diabetes- and obesity-associated nephropathy, will affect the development of early renal injury in OZR possibly via alteration of AGEs formation. The OZR were left without exercise (sedentary) or subjected to 10 weeks intermittent treadmill running of moderate intensity. Compared with sedentary OZR, kidneys of running OZR had significantly less glomerular mesangial expansion and tubulointerstitial fibrosis. Running OZR had significantly lower plasma AGEs-associated fluorescence and N(epsilon)-carboxymethyllysine. Correspondingly, renal AGEs and N(epsilon)-carboxymethyllysine content were lower in running OZR. Systemically, exercise increased aerobic metabolism, as apparent from urinary metabolite profiling. No differences in plasma glucose, insulin, or lipid profile were found between the 2 groups. Apart from lower advanced oxidation protein products (a marker of myeloperoxidase activity), no other marker of inflammation was altered by exercise, either systemically or locally in kidneys. No indication of changed oxidative status was revealed between the groups. Exercise in OZR decreased advanced glycation. This might represent the early event of exercise-induced renoprotection in diabetic nephropathy in OZR. If confirmed in clinical studies, regular moderate exercise could represent an easy and effective nonpharmacologic approach to reduce advanced glycation.
