Search PubMed⌕ Search

Biomedical subjects

L Kaczmarek

Publications and source records attributed to L Kaczmarek.

142 records · Page 8Linked to original sources
PubMedDate not supplied

A backcross method to prevent prenatal death of steel mutant mice.

Homozygous Sl/Sl mice survive until adulthood when obtained from matings between WC/Re-Sl/+ and (WC/Re X Swiss:NIH) F1-Sl/+ or WC/Re-Sl/+ and (WC/Re X AKR/Cum) F1-Sl/+ mice. They possess the classical hematological abnormalities produced by mutations at the Sl locus.

Animals↗
PubMedDate not supplied

Tactile experience induces c-fos expression in rat barrel cortex.

Understanding gene expression that is responsive to sensory stimulation is central to elucidate molecular mechanisms underlying neuronal plasticity. In this study we demonstrate two new methods of stimulating whiskers that provide major sensory input to rat neocortex. In the first paradigm, animals were placed on the top of a cylinder and their vibrissae were brushed by hand. In the second paradigm, animals were placed for a brief period of time into a new, wired cage resulting in vibrissae stimulation when they explored the new environment. Both approaches induced c-Fos expression in barrel cortex corresponding to the stimulated vibrissae, especially in layer IV. Layers II/III and V/VI also showed c-Fos induction, but there were no detectable changes in layer VIb. The majority of c-Fos-expressing cells are probably not inhibitory neurons, because they do not show parvalbumin staining. Both paradigms, in contrast to the previous methods, are simple to use and do not require anesthesia, restraint of animals, or elaborate experimental setups.

Animals↗
PubMedDate not supplied

Microbial conversion of methyl- and methoxy- substituted derivatives of 5H-indolo[2,3-b]quinoline as a method of developing novel cytotoxic agents.

In furtherance of our structure-activity relationship studies on the antitumor activity of indolo[2,3-b]quinolines, novel cytotoxic derivatives bearing methyl groups at N-5, C-11, C-2 and/or C-9, as well as methoxy-groups at C-2 and/or C-9, were synthesized by the modified Graebe-Ullmann reaction. To elucidate the metabolic pathways of these compounds, zygomycete fungus Cunninghamella elegans ATCC 9245 (which is known to produce drug metabolites that are also formed in mammals) was used as a mimetic organism. Simultaneously, biotransformation of the same substrates was carried out with a microsomal fraction of rat liver. Three forms of microbial conversion were observed: hydroxylation of the aromatic ring or hydroxylation of the methyl group, and O-demethylation. The reaction proceeded regioselectively, and only positions C-2 and C-9 were affected in the indolo[2,3-b]quinoline system. The products formed were found to be identical with the metabolites generated by rat liver microsomes. The metabolites obtained displayed a cytotoxic activity in vitro against colon adenocarcinoma SW-707 and lung carcinoma A-549 (ID50 in the range 0.27-3.04 microM), which was as strong as that of the substrates. In the course of the further metabolic pathway study of indolo[2,3-b]quinolines we found that metabolites with a hydroxyl group in the aromatic system were transformed to non-cytotoxic polymeric products by multicopper oxidases: human ceruloplasmin or fungal laccase (used as mimetic enzyme), whereas metabolites with a hydroxymethyl group did not undergo such bioconversion. The last mentioned compounds can be regarded as a novel type of cytotoxic indolo[2,3-b]quinoline derivatives formed in metabolic processes.

Animals↗
PubMedDate not supplied

Synthesis and pharmacological properties of some dipyrido[1,3]diazepinones.

The synthesis of two isomeric dipyrido[1,3]diazepinones (3a,4) and N-monosubstituted derivatives of 3a by cyclocondensation of corresponding bipyridinediamines (1, 2) with urea was described. The alkylation of 3a and 4 with alkyl halides 6 in K2CO3/DMF/TBAB system gave N,N'-disubstituted compounds 7 and 8. Dipyrido[1,3]diazepinones 8a and 3b-d showed a weak general depressive action on the central nervous system and they were also devoid of antidepressant, anxiolytic, anticonvulsant and serotoninolytic or serotoninomimetic properties.

Analgesics↗
PubMedDate not supplied

Synthesis and pharmacological properties of 13H-naphtho[1',2':7,6] [1,4] diazepino[2,3-b] pyridines.

The synthesis and properties of 13H-naphtho[1',2':7,6] [1,4] diazepino[2,3-b] pyridines (7a--g) were described. New compounds were studied in rats and in mice in the tests used for preclinical assessment of antidepressant or anxiolytic activity. Compound 7c showed weak antagonism towards the reserpine-induced hypothermia and shortened immobility time in the despair test. None of the tested compounds had an anxiety-relieving action.

Animals↗
PubMedDate not supplied

Synthesis and pharmacological properties of some derivatives of 3-phenylimidazo[4,5-b]pyridine.

The one-pot synthesis and properties of some derivatives of 3-phenylimidazo [4,5-b]pyridine (4a-g) were described. The central action of compounds 4a, 4f and 4g has been investigated using behavioral tests in mice and rats. The tested compounds showed a potent sedative effect. Compound 4f has central serotoninolytic properties in the m-CPP induced hyperthermia in rats.

Analgesics↗
PubMedDate not supplied

Cancerostatics. IV. On the synthesis of some noval 1-Azacarbazole derivatives as antineoplastic agents.

By condensation of 2-chloro-3-nitropyridine with some anilines the corresponding 2-anilino-3-nitropyridines 1a--11 were obtained. Hydrogenation of these compounds and subsequent diazotization of the 2-anilino-3-aminopyridine derivatives 2a--2l gave triazoles 3a--3l which thermally decomposed in PPA or in liquid paraffine afforded the required 6- and 8-substituted 1-azacarbazole derivatives 4a--3, i--l. Some of these compounds showed significant activity against transplanted mouse sarcoma 180. None of them were active against L 1210 and P 388 leukemias.

Animals↗
PubMedDate not supplied

Cancerostatica. I. synthesis of some pyrazolo[1,5-a]pyrimidine and pyrazolo [3,4-b] pyridine derivatives.

In basic medium 2-phenyl-and 2-(pyridyl-4')-derivatives of 3-dimethylaminoacrlein yields with 5-aminopyrazol-3-one the corresponding pyrazolo [1,5-a] pyrimidines. However, in acid medium, 2-phenyl-3-dimethylaminoacrolein cyclised to derivatives of pyrazolo[3,4-b] pyridine. A reaction mechanism is proposed. Some of these compounds showed significant cytostatic activity against transplanted Ehrlich asc. carcinoma and Nemeth-Kellner lymphoma.

Animals↗
PubMedDate not supplied

Cancerostatica. II. Synthesis and preliminary cytostatic screening of some alpha-carboline derivatives.

6-Phenyl-and (6-pyridyl-3')-2-chloro-3-aminopyridines were transformed by treatment with HNO3 into the corresponding pyrido [4,5-b] triazoles [7,8]. In PPA medium at 180 degrees, triazoles 7 and 8 decompose to 2-substituted alpha-carbolines 9,10 and anilino-3-hydroxypyridines 11, 12. Some of these compounds showed significant cytostatic activity against transplanted Ehrlich ascites carcinoma and Nemeth-Kellner lymphoma.

Animals↗
PubMedDate not supplied

Methoxy- and methyl-, methoxy-5,6,11-trimethyl-6H-indolo [2,3-b]quinolinium derivatives as novel cytotoxic agents and DNA topoisomerase II inhibitors.

New members of the cytotoxic indolo[2,3-b]quinoline family, with a methyl groups at N-5, N-6 (their presence stabilizes the positive charge of the molecule), were prepared using a modified Graebe-Ullmann reaction. The derivatives obtained were well soluble in water in a non-pH-dependent manner. They displayed strong antimicrobial activity against Gram-positive bacteria and pathogenic fungi (the MIC values fall between 0.0025 and 0.12 mM) and highly selective cytotoxicity in vitro against different human cancer cell lines: colon adenocarcinoma SW 707, lung carcinoma A 549, transitional cell carcinoma Hu 1703, and oral epidermoid carcinoma KB, in the range of 0.01 to 3.0 microM. They also stimulated the formation of topoisomerase-II-mediated DNA cleavage at concentration from 0.04 to 0.5 microM. These observations correspond well with the ability of the tested compounds to increase the melting temperature of calf thymus DNA (delta Tm being between 13 degrees C and 22 degrees C).

Animals↗