naphthoquinones and phthiocol

Novel phthiocol-based organometallics with in situ formed tridentate N,O,O-coordination motif were established via three-component microwave assisted one-pot reaction. These complexes exhibited enhanced stability in aqueous solution compared to the parental compound KP2048 and showed unexpected cytotoxic behaviour and selectivity in 2D and 3D cell cultures.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Models, Molecular; Molecular Structure; Naphthoquinones; Organometallic Compounds; Structure-Activity Relationship

The quinoid pigments pthiocol, produced by Mycobacterium tuberculosis, and pyocyanine, produced by Pseudomonas aeruginosa, were examined for their effects on O2.- production in cultured human lung epithelial-like A549 cells. Intracellular O2.- levels were measured using the O2.-sensitive aconitase(s), and rates of O2.- generation were assessed from rates of antimycin-resistant respiration. Elevated O2.- was detected in cells exposed to < 25 microM phthiocol and < 2 microM pyocyanine in neutral pH medium, and both agents impaired cell growth. The O2.- scavenging manganoporphyrin, Mn(III)TMPyP, partially protected cells against pyocyanine and phthiocol-mediated growth inhibition. O2.- production by phthiocol and pyocyanine was enhanced by acidification of the growth medium. Surprisingly, the dicumarol-inhibitable quinoid detoxification enzyme DT-diaphorase was a significant source of phthiocol and pyocyanine-mediated O2.- generation in cells. O2.- production in macrophages by the phthiocol analog, menadione, was shown to impair macrophage mitochondrial respiration and bactericidal activity toward Escherichia coli. Phthiocol and pyocyanine, by producing O2.-/H2O2, and inhibiting host cell aconitase activity, energetics, and other host cell functions, may contribute to the pathogenicity of M. tuberculosis and P. aeruginosa.

Topics: Aconitate Hydratase; Antimycin A; Cell Division; Cell Line; Dicumarol; Free Radical Scavengers; Humans; Hydrogen-Ion Concentration; Lung; Macrophages; Metalloporphyrins; Mycobacterium tuberculosis; Naphthoquinones; Oxygen Consumption; Pigments, Biological; Pseudomonas aeruginosa; Pyocyanine; Superoxides; Vitamin K

MaciasR, Frank M. (Northrop Corporation, Hawthorne, Calif.). Phthiocol and menadione as acetate-replacing factors for Lactobacillus delbrueckii. J. Bacteriol. 82:657-661. 1961.-Lactobacillus delbrueckii (ATCC 9649), when cultured under nitrogen, or in ferrous iron-containing media exposed to air, requires, for the initiation of growth, compounds that are known to behave as electron acceptors. The ferrous iron probably induces what amounts to anaerobic conditions; that is, it blocks access of the organism to oxygen. Several electron carriers, such as methylene blue and naphthoquinones, stimulate growth of the organism in acetate-free media exposed to air. The most active acetate-replacing agent found is phthiocol. Methylene blue does not stimulate growth under nitrogen. It is suggested that the naphthoquinones bring about the initial oxidations required for growth by transferring the electrons to some other constituent of the medium. Growth of the organism in acetate-free media under CO(2) indicates that CO(2) or its fixation product can behave also as an initial oxidant.

Topics: Acetates; Iron; Lactobacillus; Lactobacillus delbrueckii; Naphthoquinones; Nitrogen; Oxidation-Reduction; Oxygen; Vitamin K; Vitamin K 3

Topics: Humans; In Vitro Techniques; Mycobacterium tuberculosis; Naphthoquinones

Topics: Biochemical Phenomena; Biochemistry; Naphthoquinones; Nitrogen; Pigments, Biological

Topics: Bacteria; Growth; Mycobacterium; Naphthoquinones; Physiological Phenomena

Topics: Anti-Bacterial Agents; Bacillus; Bacteria; Humans; Indoles; Mycobacterium tuberculosis; Naphthoquinones; Pigments, Biological; Prodigiosin