ABSTRACT
Two ink genes, inkO and inkD, responsible for the earliest steps of K252a biosynthetic pathway, from Nonomurea longicantena JCM 11136 were heterologously coexpressed in Streptomycesalbus J1074. The resultant strain accumulated compound that was purified by HPLC and studied by NMR. Coexpression of inkOD yielded chromopyrrolic acid, the key intermediate in an indolocarbazole biosynthesis.
Subject(s)
Carbazoles/pharmacology , Chemistry, Pharmaceutical/methods , Indole Alkaloids/pharmacology , Pyrroles/chemistry , Streptomyces/metabolism , Carbazoles/chemical synthesis , Carbazoles/chemistry , Chromatography, High Pressure Liquid , Chromatography, Liquid/methods , Drug Design , Indole Alkaloids/chemical synthesis , Magnetic Resonance Spectroscopy , Mass Spectrometry/methods , Models, Chemical , Multigene Family , Tryptophan/chemistryABSTRACT
Chemical investigations of the tropical marine sponge Hyrtios sp. have resulted in the isolation of a new alkaloid, 1-carboxy-6-hydroxy-3,4-dihydro-beta-carboline (1) together with the known metabolites, 6-hydroxy-3,4-dihydro-1-oxo-beta-carboline (2), 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (3), serotonin (4), hyrtiosin A (5), 5-hydroxyindole-3-carbaldehyde (6), and hyrtiosin B (7). Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data. Hyrtiosin B (7) displayed a potent inhibitory activity against isocitrate lyase (ICL) of Candida albicans with an IC(50) value of 89.0 microM.
Subject(s)
Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Candida albicans/enzymology , Carbolines/isolation & purification , Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , Isocitrate Lyase/antagonists & inhibitors , Porifera/chemistry , Animals , Antifungal Agents/chemistry , Carbolines/chemistry , Carbolines/pharmacology , Indole Alkaloids/chemistry , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
A series of halophenols was prepared by the reaction of bis(hydroxyphenyl)methanes with effective halogenating agents such as bromine and sulfuryl chloride. One of these compounds, a biologically active halophenol--2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (1)--frequently isolated from red algae, was synthesized for the first time. Other halophenols included several novel compounds, together with known derivatives that were synthesized from the phenolic intermediates, bis(3,4-dihydroxyphenyl)methane (5) and bis(2-hydroxyphenyl)methane (14). All of the synthesized compounds were tested for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. The preliminary structure-activity relationship was investigated in order to determine the essential structural requirements for their antimicrobial activity. Of all these halophenols, 2,2',3,3',6-pentabromo-4,4',5,5'-tetrahydroxydiphenylmethane (8) was found to be the most active against Candidaalbicans, Aspergillusfumigatus, Trichophytonrubrum, and Trichophytonmentagrophytes while 3,3',5,5'-tetrachloro-2,2'-dihydroxydiphenylmethane (18) exerted a powerful antibacterial effect against Staphylococcusaureus, Bacillussubtilis, Micrococcusluteus, Proteusvulgaris, and Salmonellatyphimurium.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Chemistry, Pharmaceutical/methods , Methane/chemistry , Phenol/chemistry , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemistry , Chlorophenols/chemistry , Drug Design , Halogens/chemistry , Microbial Sensitivity Tests , Models, Chemical , Phenols/chemistryABSTRACT
Seven sesterterpene sulfates (1-7) were isolated from the tropical sponge Dysidea sp. and their inhibitory activities against isocitrate lyase (ICL) from Candida albicans were evaluated. Among the isolated natural products compound 6 and 7 were found to be strong ICL inhibitors. The isolated compounds (1-7) also showed potent antibacterial effect against Bacillus subtilis and Proteus vulgaris, but did not display antifungal activity.
