Biomedical subjects
Publications and source records attributed to J W Westley.
Two novel spirosesquiterpene aldehydes, corallidictyals A [1] and B [2], were isolated as a mixture from the marine sponge Aka (= Siphonodictyon) coralliphagum, and their structures were determined by detailed spectroscopic methods. These compounds were identified in a screen for inhibitors of protein kinase C.
A novel epoxide, in addition to eight known diterpenes, has been isolated from a marine brown alga of the genus Dictyota. The structures of these compounds were established by the interpretation and comparison of spectral data with literature data. Most of the isolates demonstrated vasopressin receptor antagonist activity in vitro with the new epoxide being the most active of the diterpenes tested.
Two novel pyrrolidine compounds, conioidines A [1] and B [2], have been isolated from the Texas plant, Chamaesaracha conioides (Solanaceae). Their structures were determined by spectroscopic methods and hydrolysis studies. Both natural products, like doxorubicin, showed DNA-specific KB cell cytotoxicity. Dose-response data indicated a Kd value of 2.8 microM for binding of conioidine A [1] to calf thymus DNA.
Two new glycosides have been isolated from the MeOH extract of the stem wood and stem bark of an Ecuadorian plant Chamaedorea linearis, and their structures have been determined by spectroscopic means and X-ray analysis of the aglycone to be 1-O-[beta-L-fucopyranosyl-(4'-sulfate)]-25R,5 alpha-spirostane-1 beta, 3 beta-diol [1]) and 1-O-[beta-L-fucopyranosyl-(4'-sulfate)]-25R,5 alpha-spirostane-1 alpha, 3 beta-diol [2]. These compounds were identified in a screen for inhibitors of recombinational DNA repair. Cytotoxic activity was also demonstrated.
Antibiotic X-14889A, C, and D are novel polyether antibiotics related to lysocellin and antibiotic X-14873A. They are produced by a streptomycete isolated from a soil of Wisconsin. The antibiotic X-14889C is active against Gram-positive bacteria and exhibits ionophore property.
Streptomyces sp. X-14889 (NRRL 15517) has been found to produce a number of novel polyether antibiotics and an orange pigment. One of the antibiotics, X-14889B (3) was identified as ferensimycin A, which in turn is an isomer of the well-studied polyether antibiotic, lysocellin (1). Of the three other antibiotics, X-14889C (4) is a lower homolog of ferensimycin A and antibiotics X-14889A (2) and D (5) which are respectively the descarboxy and anhydro-descarboxy forms of this same molecule. The latter compound, X-14889D is of interest as it contains an ether bridge across the terminal tetrahydrofuranyl ring in an analogous relationship to that reported earlier for antibiotics X-14873A (6) and G.
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Three new imidazole alkaloids, leucettamines A [1] and B [2] and leucettamidine [3], have been isolated from the Palauan sponge Leucetta microraphis. Their structures were established on the basis of extensive spectral analyses. Leucettamine A showed potent leukotriene B4 receptor binding activity (K(i) = 1.3 microM), while leucettamine B was essentially inactive (K(i) = 100 microM) and leucettamidine showed significant activity (K(i) = 5.3 microM). With leucettamine A identified as a pure LTB4 receptor antagonist, a new structure lead is presented to inflammation therapy.
The EtOAc extract of the sponge Xestospongia muta collected in Colombus Island, Bahamas, yielded eleven straight-chain unsaturated, polyacetylenic, brominated acids, seven of which were identified on the basis of spectral data, including the unknown acids 2-7. These acetylenic acids are the first known examples that have been shown to inhibit HIV protease, a critical enzyme in the replication of human immunodeficiency virus.
Streptomyces sp. X-14873 (ATCC 31679) has been found to produce a number of secondary metabolites. Three have been identified as the novel actinomycins, X-14873B, C and D, each of which contains both proline and 3-hydroxy-5-methylproline. Potentially, the most important microbial product from this fermentation is the novel polyether antibiotic X-14873A which differs from lysocellin only in the substituents at carbons C-4 and C-5 in the tetrahydropyranyl ring. The methyl group and proton in lysocellin are replaced by an ethyl and hydroxyl group, respectively in X-14873A. In addition, two other novel polyethers, X-14873H and G, were isolated and shown to differ from 1 in lacking a carboxyl group and in the case of 3, possessing an ether bridge across the terminal tetrahydrofuranyl ring system.
Novel polyether antibiotics X-14873A, X-14873G, and X-14873H are produced by the fermentation of Streptomyces sp. X-14873 (ATCC 31679). This report presents taxonomic studies and fermentation conditions for the antibiotic producing culture. The antibiotics are mainly active against Gram-positive bacteria. The ionophore properties of X-14873A are also characterized.
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Antibiotic X-14885A is a novel divalent cation ionophore produced by a Streptomyces culture isolated from soil sample collected in Wyoming. Its cation binding sequence has been found to be: Mg2+ greater than Ca2+, Sr2+ greater than Ba2+ much greater than Li+, Na+, Rb+, K+, Cs+.
Conversion of the monovalent polyether antibiotic monensin into a series of urethane derivatives substituted at C-26 causes a ten-fold increase in the cation transporting properties of the antibiotic as well as making the resulting semisynthetic urethanes divalent ionophores. These changes must in part account for the enhanced antimicrobial activities of the urethanes. The most active derivatives are the phenylurethanes which are ten times more active in vitro against Gram-positive bacteria and unlike monensin are active against Candida albicans and Penicillium digitatum. Another novel activity exhibited by four of the urethanes was against Plasmodium berghei, the causative agent for malaria.
Antibiotic X-14885A is a polyether antibiotic belonging to the class of these natural acid ionophores known as pyrrolethers. The structure of the antibiotic was elucidated by X-ray crystallographic analysis of the hydrated sodium salt, which crystallized as a tetramer containing four antibiotic and water molecules and four atoms of sodium. Antibiotic X-14885A differs from the most well-known member of the class, A-23187, in two respects: the aromatic N-methylamino group present in the latter is replaced by a phenolic hydroxyl, and one of the four aliphatic methyls is replaced by a proton. Antibiotic X-14885A is active against Gram-positive bacteria and the spirochete, Treponema hyodysenteriae.
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