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Transgenic bacteria producing pyrroloquinoline quinone, a known cofactor for dehydrogenases and an inducer of a periplasmic protein kinase activity, show resistance to both oxidative stress and protection from nonoxidative effects of radiation and DNA-damaging agents. Deinococcus radiodurans R1 encodes an active pyrroloquinoline quinone synthase, and constitutive synthesis of pyrroloquinoline quinone occurred in wild-type bacteria. Disruption of a genomic copy of pqqE resulted in cells that lacked this cofactor. The mutant showed a nearly 3-log decrease in [gamma], radiation resistance and a 2-log decrease in mitomycin C tolerance compared to wild-type cells. The mutant cells did not show sensitivity to UVC radiation. Expression of pyrroloquinoline quinone synthase in trans showed that there was functional complementation of [gamma] resistance and mitomycin C tolerance in the pqqE mutant. The sensitivity to [gamma], radiation was due to impairment or slow kinetics of DNA double strand break repair. Low levels of [sup.32]p incorporation were observed in total soluble proteins of mutant cells compared to the wild type. The results suggest that pyrroloquinoline quinone has a regulatory role as a cofactor for dehydrogenases and an inducer of selected protein kinase activity in radiation resistance and DNA strand break repair in a radioresistant bacterium.

Research has been conducted on the cis- and trans-disubstituted octahydroquinolinone ring systems with stereogenic centers. The stereodivergent synthesis of these systems has been carried out via the stereodivergent and stereoselective construction of trisubstituted piperidine ring systems using Michael addition reaction to enaminoesters.

Research has been conducted on the ferriprotoporphyrin IX heme mu-oxo dimers and aminoquinolinal antimalarial drugs. The solution structures formed between these compounds at different pH have been investigated via the use of paramagnetic relaxation effects in determining the distance constraints for these solution structures and the details are reported.

Research has been conducted on 7-alkylamino-2-methylquinoline-5,8-diones. The synthesis of these diones carried out from 2,5-dimethoxyaniline via the Sakraup reaction, demethylation, oxidative bromination, amination and debromination is described.

Research has been conducted on the zinc-acetic acid couple. The obtention of the pentacyclic skeletons via the zinc-acetic acid couple reaction with substituted quinolines is described.

Research has been conducted on the mixed ligand ruthenium(II) phosphine 2-(2'-pyridyl)quinoline complexes. The preparation of these complexes from phosphine and Ru(pq) (sub)2 Cl (sub)2 is described.

Research has been conducted on the isomeric 5-, 6-, 7-, 8-hydroxyquinolines and 5-hydroxyisoquinoline. The results of the superelectrophilic activation of these compounds by their reaction with cyclohexane and benzene are presented.

In the tryptophan-niacin conversion, 2-amino-3-carboxymuconate-6-semiardehyde decarboxylase (ACMSD; formerly termed picolinic carboxylase) is an important enzyme regulating the generation of quinolinate. In a series of experiments, we investigated alterations of ACMSD expression in rats by feeding a high protein diet and by inducing diabetes with streptozotocin (STZ). Male Sprague-Dawley rats (5-wk-old) were fed a diet containing 40% casein for 11 d, and hepatic ACMSD activity and mRNA expression were determined at intervals. The enzyme activity had increased at d 2, and it continued to increase through d 11. ACMSD mRNA expression had increased at d 1 and the elevated levels were maintained through d 11. Shifting from the 40% casein diet to a 20% casein diet restored hepatic ACMSD activity and mRNA expression to normal levels within 5 d and 2 d, respectively. In another series of experiments, male Wistar rats were injected with STZ (50 mg/kg) and the time-course (d 0, 1, 2, 4, 8 and 14) of the change in hepatic ACMSD activity and mRNA expression were examined. The activity increased dramatically after d 4, while mRNA expression was significantly elevated at d 2, followed by slight increases through d 14. Insulin administration (2 U/12 h) reduced the elevated ACMSD activity and fully suppressed the elevated ACMSD mRNA expression due to STZ injection. These results indicated that the fluctuation of hepatic ACMSD mRNA expression was followed by that of ACMSD activity. KEY WORDS: * 2-amino-3-carboxymuconate-6-semiardehyde decarboxylase * tryotophan-niacin metabolism * high protein diet * streptozotocin-diabetes * rats

Research has been conducted on the tert-butyl imines of o-(1-alkenyl)benzaldehydes and analogues. Results indicate that the electrophilic cyclization of these imines provides the synthesis of a variety of substituted isoquinolines.

Research has been conducted on the indole and quinoline derivatives. The preparation of these derivatives from the nitrogen-tethered 2-methoxyphenols carried out via the use of phenyliodine(III) diacetate mediated oxidative acetoxylation and the following intramolecular nucleophilic addition reaction is discussed.

The authors review the publications on the antitumor antibiotics belonging to the tetrahydroisoquinoline family. The topics of interest include the antitumor and antimicrobial activities of these antibiotics and other biological properties.

Research has been conducted on the 7-acetyl-4,6-dimethoxy-3-phenylindole. The conversion of this compound into 7-indolyl chalcones via the reaction with aryl aldehyde has been carried out and the details are reported.

Research has been conducted on the cyclopropane amino acids and their derivatives. The study of the cyclopropanation mechanism has been carried out and the results are presented.

Telomeres of human chromosomes contain a G-rich 3'-overhang that adopts an intramolecular G-quadruplex structure in vitro which blocks the catalytic reaction of telomerase. Agents that stabilize G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalyzed by telomerase and can therefore act as antitumor agents. We have identified by Fluorescence Resonance Energy Transfer a new series of quinoline-based G-quadruplex ligands that also exhibit potent and specific anti-telomerase activity with I[C.sub.50] in the nanomolar concentration range. Long term treatment of tumor cells at subapoptotic dosage induces a delayed growth arrest that depends on the initial telomere length. This growth arrest is associated with telomere erosion and the appearance of the senescent cell phenotype (large size and expression of [beta]-galactosidase activity). Our data show that a G-quadruplex interacting agent is able to impair telomerase function in a tumor cell thus providing a basis for the development of new anticancer agents. telomerase inhibitor | tetraplex | drug-DNA recognition

Research has been conducted on the monosubstituted isoquinolines and pyridines. The preparation of these compounds has been carried out via the terminal acetylene coupling with the o-iodobenzaldehydes' tert-butylimines and 3-halo-2-alkenals in the presence of the palladium catalyst and the details are presented.

Research has been conducted on the amides derived from the gulonic acid. The results of the diastereoselective alkylation of these amides are reported.

Research has been conducted on the thioether complexes with formula Delta/Lambda-chloro(thioether)bis(2,2'-bipyridine)metal(II) where M = Ru, Os; thioether = dimethyl sulfide, diethyl sulfide and tetrahydrothiophene. The synthesis of these complexes has been performed and the use of the spin-inversion transfer and line-shape NMR methods in measuring the inversion rate at the thioether ligand sulfur atom is described.

Research has been conducted on the analogues of conformationally constrained didemnin B. The design and synthesis of this analogue are described and the results indicate that the conformation of the didemnin B [N,O-Me (sub)2 Tyr (super)5] residue matches the conformation imposed by the L-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid replacement.

Research has been conducted on the cyclometalation process. The cyclometalation of 1-(2'-quinolinyl)pyrene and 1,3-(2'-quinolinyl)pyrene with ruthenium(II) has been investigated and the results are presented.

Research has been conducted on the 3,3'-polymethylene bridged ligands. The use of the Friedlander condensation in the synthesis of these ligands is described.

Research has been conducted on the cis-dibenzoquinolizinium propanols. The stereoselective preparation of these propanols and their transformation into bis- and mixed-onium chlorofumarates are described.

Research has been conducted on the substituted tetrahydroquinoline-4-carboxylic esters. The diastereoselective synthesis of these esters developed from methyl (2-nitrophenyl)acetate is described.

Research has been conducted on the quinoline-type NADH model compounds. Results demonstrate that these compounds have unannulated amide moieties with simple structures.

The catalytic role of calcium ions for the oxidation of alcohols by coenzyme PQQ (4,5-dihydro-4,5-dioxo-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid) was investigated. The trimethyl ester of PQQ was synthesized by esterification of the coenzyme in methanol to demonstrate the methanol oxidation by the calcium complex of PQQ as well as the redox mechanism of the calcium-containing quinoprotein alcohol dehydrogenases. The addition-oxidative elimination mechanism through the C-5 hemiacetal intermediate is proposed.

Pyrroloquinoline quinone (PQQ) is proposed as a nutritionally important growth factor, and we provide evidence that PQQ improves reproduction performance in BALB/c mice and stimulates neonatal growth. In the first experiment, weanling female BALB/c mice were adapted to a chemically-defined diet containing 0, 100, 200, 300, 1000, or 5000 ng PQQ/g of diet. The mice were bred and their reproductive performance and surviving offspring were assessed for 20-wk. Reproductive outcome was markedly compromised for the groups most deprived of PQQ. Supplemented groups (greater than or equal to 1000 ng PQQ/g diet) had 8 pups/litter compared with 4-5 pups/litter in the PQQ-deprived groups (less than or equal to 300 ng PQQ/g diet). Of the pups surviving to weaning, 8 of 10 survived when PQQ was added to the diet (greater than or equal to 300 ng PQQ/g diet) compared with 4 of 10 in the PQQ-deficient group. The apparent requirement for PQQ for optimal growth of surviving neonates was estimated to be greater than or equal to 300 ng PQQ/g of diet. Moreover, splenic cell response to the mitogens concanavalin A and lipopolysaccharide, appeared related to PQQ intake. In a second experiment, female BALB/c mice were fed diets containing PQQ added at 0 or 1000 ng/g of diet, and interleukin 1 and 2 production were assessed. In particular, levels of interleukin 2, an autocrine and paracrine growth factor, were reduced in mice fed the deficient diet at a time when T-cell proliferation occurs in neonates. Results suggest that PQQ or similar compounds may play nutritionally important roles at critical stages in development.

Enrichment cultures of pseudomonads capable of transforming or degrading quinolines were established from creosote-contaminated soil. The selected bacteria were able to degrade quinoline, isoquinoline and 6-methylquinoline in reactions which produced monohydroxylated metabolites. In addition, the quinoline-degrading microorganisms retained their degradative ability in aqueous and nonaqueous immobilized-cell systems.

Research has been conducted on the aromatic amines and cyclic ethers. The synthesis of different tetrahydroquinoline derivatives carried out via the use of the domino reaction of these aromatic amines and cyclic ethers is described.

Research has been conducted on the reductive cyclization of enones. The mechanism for transformation of the nitro ketone into tetrahydroquinoline via the tris(dimethylamino)-methane treatment in explaining the reductive cyclization of alpha'-(2-nitrophenyl) enones is described.

The authors have investigated superoxide scavenging by different prenyllipids in thylakoid membranes. The results have demonstrated that these prenyllipids possess superoxide scavenging properties, and that in this respect plastoquinol-9 has been the most active.