Aristolactams, 1-(2-C-methyl-beta-D-ribofuranosyl)-uracil and other bioactive constituents of Toussaintia orientalis.

The new aristolactam alkaloid toussalactam {2-hydroxy-1,6-dimethoxy-5H-dibenzo[cdf]indol-4-one} and the known ones, namely aristolactam AII, aristolactam BII, piperolactam C and aristolactam FII; 1-(2-C-methyl-beta-D-ribofuranosyl)-uracil, 3,4,5-trimethoxyphenyl-beta-D-glucopyranoside, and three catechinoids were isolated from the cytotoxic Toussaintia orientalis Verdc stem and root bark extracts, and their structures established based on analysis of spectroscopic data. The aristolactams exhibited antimicrobial and antiinflammatory activity, aristolactam FII showing almost the same level of activity as the standard anti-inflammatory agent Indomethacin. The compounds also exhibited either mild or no antiproliferative and cytotoxic activities, except aristolactam FII that showed the same level of cytotoxicity as the standard drug Camptothecin. 1-(2-C-Methyl-beta-D-ribofuranosyl)-uracil, which is being reported for the first time as a natural product, was inactive in the antibacterial, antifungal, antiinflammatory, antiproliferative and cytotoxicity assays.

Cytotoxic, anti-proliferative and antimicrobial furanoditerpenoids from Stuhlmania moavi.

The furanoditerpenoids voucapane, voucapane-6alpha,7alpha-diol, voucapane-18,19-diol and 18-hydroxyvoucapan-19-al were isolated from the cytotoxic stem and root bark extracts of Stuhlmaniamoavi Verdc. (Ceasalpiniaceae) and their structures established based on analysis of spectroscopic data. The compounds exhibited anti-proliferative, cytotoxic, antibacterial and antifungal activities, 18-hydroxyvoucapan-19-al showing the highest anti-proliferative and cytotoxic properties. Voucapane-18,19-diol was only mildly active but the activity was enhanced for its 18,19-di-(4-methyl)-benzenesulphonate. Some of these results thus corroborate the traditional medicinal uses of the crude extracts for the treatment of skin infections.

The Pseudomonas aeruginosa pirA gene encodes a second receptor for ferrienterobactin and synthetic catecholate analogues.

Actively secreted iron chelating agents termed siderophores play an important role in the virulence and rhizosphere competence of fluorescent pseudomonads, including Pseudomonas aeruginosa which secretes a high affinity siderophore, pyoverdine, and the low affinity siderophore, pyochelin. Uptake of the iron-siderophore complexes is an active process that requires specific outer membrane located receptors, which are dependent of the inner membrane-associated protein TonB and two other inner membrane proteins, ExbB and ExbC. P. aeruginosa is also capable of using a remarkable variety of heterologous siderophores as sources of iron, apparently by expressing their cognate receptors. Illustrative of this feature are the 32 (of which 28 putative) siderophore receptor genes observed in the P. aeruginosa PAO1 genome. However, except for a few (pyoverdine, pyochelin, enterobactin), the vast majority of P. aeruginosa siderophore receptor genes still remain to be characterized. Ten synthetic iron chelators of catecholate type stimulated growth of a pyoverdine/pyochelin deficient P. aeruginosa PAO1 mutant under condition of severe iron limitation. Null mutants of the 32 putative TonB-dependent siderophore receptor encoding genes engineered in the same genetic background were screened for obvious deficiencies in uptake of the synthetic siderophores, but none showed decreased growth stimulation in the presence of the different siderophores. However, a double knock-out mutant of ferrienterobactin receptor encoding gene pfeA (PA 2688) and pirA (PA0931) failed to be stimulated by 4 of the tested synthetic catecholate siderophores whose chemical structures resemble enterobactin. Ferric-enterobactin also failed to stimulate growth of the double pfeA-pirA mutant although, like its synthetic analogues, it stimulated growth of the corresponding single mutants. Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. The example of these two enterobactin receptors probably illustrates a more general phenomenon of siderophore receptor redundancy in P. aeruginosa.