Iodine-mediated oxidative cyclization for one pot synthesis of new 8-hydroxyquinaldine derivatives containing a N-phenylpyrazole moiety as pesticidal agents.

In continuation of our research aimed at discovery and development of new pesticidal agents, a series of new 8-hydroxyquinaldine derivatives containing a N-phenylpyrazole moiety were prepared and their structures were characterized by 1H NMR, IR, ESI-MS and mp. Meanwhile, an efficient way of using iodine-mediated oxidative cyclization for one pot synthesis of these 8-hydroxyquinaldine derivatives containing a N-phenylpyrazole moiety was developed. The bioassay showed that compounds 8g and 9f exhibited potent pesticidal activities against both Mythimna separata Walker and Plutella xylostella Linnaeus. The structure-activity relationships were also discussed.

Complete genome sequence and metabolic potential of the quinaldine-degrading bacterium Arthrobacter sp. Rue61a.

BACKGROUND: Bacteria of the genus Arthrobacter are ubiquitous in soil environments and can be considered as true survivalists. Arthrobacter sp. strain Rue61a is an isolate from sewage sludge able to utilize quinaldine (2-methylquinoline) as sole carbon and energy source. The genome provides insight into the molecular basis of the versatility and robustness of this environmental Arthrobacter strain. RESULTS: The genome of Arthrobacter sp. Rue61a consists of a single circular chromosome of 4,736,495 bp with an average G + C content of 62.32%, the circular 231,551-bp plasmid pARUE232, and the linear 112,992-bp plasmid pARUE113 that was already published. Plasmid pARUE232 is proposed to contribute to the resistance of Arthrobacter sp. Rue61a to arsenate and Pb2+, whereas the linear plasmid confers the ability to convert quinaldine to anthranilate. Remarkably, degradation of anthranilate exclusively proceeds via a CoA-thioester pathway. Apart from quinaldine utilization, strain Rue61a has a limited set of aromatic degradation pathways, enabling the utilization of 4-hydroxy-substituted aromatic carboxylic acids, which are characteristic products of lignin depolymerization, via ortho cleavage of protocatechuate. However, 4-hydroxyphenylacetate degradation likely proceeds via meta cleavage of homoprotocatechuate. The genome of strain Rue61a contains numerous genes associated with osmoprotection, and a high number of genes coding for transporters. It encodes a broad spectrum of enzymes for the uptake and utilization of various sugars and organic nitrogen compounds. A. aurescens TC-1 is the closest sequenced relative of strain Rue61a. CONCLUSIONS: The genome of Arthrobacter sp. Rue61a reflects the saprophytic lifestyle and nutritional versatility of the organism and a strong adaptive potential to environmental stress. The circular plasmid pARUE232 and the linear plasmid pARUE113 contribute to heavy metal resistance and to the ability to degrade quinaldine, respectively.

Application of a novel open-source program for measuring the effects of toxicants on the swimming behavior of large groups of unmarked fish.

The aim of this study was to demonstrate a novel method for measuring the effects of toxicants on the behavior of groups of unmarked fish. Ctrax is an open source Python-based machine vision program that was originally designed to track fruit flies (Drosophila). The effects of the fish anaesthetic quinaldine sulfate on the behavior of groups of 10 unmarked Arabian killifish (Aphanias dispar) in a small arena were measured. Ctrax was able to identify and track the X-Y coordinates of the individual fish over 1 min recording periods. The data was analyzed using specifically written Matlab (The Mathworks™) toolboxes and the effects of quinaldine sulfate on absolute swimming velocity, forward swimming velocity, rate of change in orientation and distance to wall were calculated. Additionally the effects of quinaldine sulfate on path tortuosity were also measured. Ctrax has significant benefits over other available technologies for tracking the 2-dimensional coordinates of fish. In particular the software is open source and thus freely available, it is accurate, requires only simple easily available equipment and able to track potentially large groups of fish (possibly >50) while maintaining their individual identities.

A study on the neurotoxicity of broxyquinoline and brobenzoxaldine combination in therapeutic doses.

The neurotoxicity of a combination of broxyquinoline and brobenzoxaldine (Intestopan Forte, containing 500 mg and 100 mg of the drugs respectively per capsule) was investigated by prospective clinical and electrophysiological studies in patients and volunteer subjects given the drugs in therapeutic doses (two capsules three times a day for 5 days). Of 16 patients with intestinal amoebiasis given the drugs (study A), 13 (81.25%) were cured. Adverse effects were mild and did not affect treatment. No neurological adverse effect was reported. Neurological examinations revealed no abnormality in any patient after treatment. Seven volunteer subjects underwent medical, neurological and ophthalmological examinations, and electrophysiological studies of ulnar and peroneal nerve conduction before and after treatment with the drugs in therapeutic doses (study B). Transient paresthesias were reported by one subject on the fourth day of treatment. No medical, neurological or ophthalmological abnormality was detected in any subject after treatment. There was no significant change in motor nerve conduction velocities. There was a significant (P less than 0.001) increase in the stimulus strength for distal ulnar stimulation and a significant (P less than 0.01) decrease in stimulus duration for proximal and distal ulnar stimulation. No significant changes were seen in the peroneal nerves in these parameters. No qualitative abnormality was seen in the oscilloscopic patterns of nerve conduction after treatment. Literature on the neurotoxicity of the halogenated hydroxyquinolines is reviewed. It is concluded that broxyquinoline and brobenzoxaldine (and probably other halogenated hydroxyquinolines as well) are safe and effective in therapeutic doses; neurotoxicity is unlikely to occur when these drugs are used according to therapeutic recommendations.

Impairment of exercise tolerance due to broxyquinoline-brobenzoxaldine combination.

A case report of impaired exercise tolerance during administration of broxyquinoline-brobenzoxaldine combination in therapeutic doses is presented. The first author of this paper, a 28-year-old healthy male, volunteered as a subject for a prospective study on the neurotoxicity of halogenated hydroxyquinolines and took a course of broxyquinoline-brobenzoxaldine combination. The author, who is a karate enthusiast, observed impairment of exercise tolerance during the course of treatment with the drugs. A challenge course of treatment with the same drugs in the same doses produced similar effects. Since halogenated hydroxyquinolines are still used widely in many countries, such an adverse effect would be of practical relevance, particularly in asymptomatic cyst-passers of Entamoeba histolytica whose occupations involve physical labour.

Tumor-initiating activity of quinoline and methylated quinolines on the skin of SENCAR mice.

Quinoline and all 7 positional isomers of methylquinoline were assayed for tumor-initiating activity on the skin of SENCAR female mice with promotion by tetradecanoyl phorbol acetate. The total initiation dose of either quinoline or the isomeric methylquinolines was 7.5 mg per mouse. Quinoline induced tumors in 53% of the mice (0.73 tumors per animal). While 2-, 3-, 5- and 7-methylquinoline did not exhibit significant tumorigenic activity in this assay, 4-methylquinoline induced tumors in 45% of the mice (0.90 tumors per animal). 8-Methylquinoline induced tumors in 45% of the mice (0.66 tumors per animal).

[Toxicity of hydroxyquinoline derivatives]. / Prouchvaniia vurkhu toksichnostta na niakoi khidroksikhinolinovi proizvodni.

We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.

Synthesis of quaternary 8-hydroxyquinoline and 8-hydroxyquinaldine-carbamates structurally related to cholinesterase.

The quaternary carbamates were synthesized by reaction of 8-hydroxyquinoline and 8-hydroxyquinaldine with alkylisocyanates, then quaternizing the carbamates produced with alkylhalides, aralkylhalides or sulphate. The UV spectra of the compounds obtained showed lambdamax at 285 nm. The new quaternary carbamates were found to be of high toxicity and parasymapathomimetic activity in white mice.