Attenuation of TNF-α secretion by L-proline-based cyclic dipeptides produced by culture broth of Pseudomonas aeruginosa.

To identify small molecule inhibitors of TNF-α, bioassay- and LC-MS-guided chemical investigation on EtOAc extract of Pseudomonas aeruginosa ABS-36 culture broth (EEPA) was performed, which yielded four proline-based cyclic dipeptides, cyclo(Gly-l-Pro) (1), cyclo(l-Pro-l-Phe) (2), cyclo(trans-4-hydroxy-l-Pro-l-Phe) (3) and cyclo(trans-4-hydroxy-l-Pro-l-Leu) (4). Compounds 1 and 3 exhibited potent inhibition of TNF-α release with IC50 values of 4.5 and 14.2µg/mL, respectively, while EEPA showed IC50 of 38.8µg/mL under lipopolysaccharide treated RAW 264.7 cell ELISA assay. Also, marked attenuation of mRNA-expression of TNF-α was shown by all compounds. In vivo testing in rats of EEPA and chemically synthesized 4 validated significant TNF-α reduction with 51% (500mg/kg) and 79% (50mg/kg), respectively. In addition, all compounds exhibited significant diminution of IL-1ß and IL-6 mRNA-expression levels and NO production. All samples displayed only weak toxicity to lipopolysaccharide-induced RAW 264.7 cells.

Isolation and characterization of antimicrobial cyclic dipeptides from Pseudomonas fluorescens and their efficacy on sorghum grain mold fungi.

This study was aimed at isolation and characterization of natural antifungal compounds for grain mold, a key parasitic fungal disease of sorghum. Pseudomonas fluorescens strain isolated from rhizosphere of groundnut crop was selected as a source. Its biocontrolling ability was assessed by testing some biochemical attributes such as phosphate-solubilization, and HCN, NH3 , indole-3-acetic acid, and siderophore production. The strain showed positive result for all except indole-3-acetic acid, revealing its suitability for a further study. The antibiotic-sensitivity pattern of the strain against 43 antibiotics was also established, which showed resistance to 15 antibiotics. The efficacy of P. fluorescens strain against grain mold was identified by dual culture technique. Hundred percent inhibition was found against Fusarium moniliforme, an important causative agent of this disease. The strain was fermented for secondary metabolites and extracted with AcOEt. Chromatographic separation of the extract yielded four known compounds, cyclo(L-Pro-L-Phe) (1), cyclo(trans-4-hydroxy-L-Pro-L-Leu) (2), cyclo(trans-4-hydroxy-L-Pro-L-Phe) (3), and cyclo(Gly-L-Pro) (4), which were characterized by spectral analysis and optical rotation. The crude extract, a mixture of 2 and 3, and isolated 1 were proved to be significantly effective against grain mold fungi. This is the first report on production of these cyclic dipeptides by P. fluorescens and their antagonistic properties.

Dodecyl α-L-rhamnopyranosyl-(1→2)-ß-D-fucopyranoside derivatives from the glandular trichome exudate of Erodium pelargoniflorum.

Chemical investigation of the glandular trichome exudate of Erodium pelargoniflorum (Geraniaceae) led to the isolation of two dodecyl disaccharide derivatives, named pelargoside A1 and pelargoside B1 (1 and 2, resp.). The structures of 1 and 2 were determined as dodecyl 4-O-acetyl-α-L-rhamnopyranosyl-(1→2)-4-O-acetyl-ß-D-fucopyranoside and dodecyl 3,4-di-O-acetyl-α-L-rhamnopyranosyl-(1→2)-4-O-acetyl-ß-D-fucopyranoside, respectively, by spectroscopic studies, including 2D-NMR, and chemical transformations. In addition, undecyl, tridecyl, and tetradecyl homologs of 1 and 2, named pelargosides A2-A4 and pelargosides B2-B4, were also characterized as minor constituents of the exudate.