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Biomedical subjects

W Raether

Publications and source records attributed to W Raether.

At least 73 records · Page 4Linked to original sources
PubMed1978

Chemotherapeutically active nitro compounds. 4.5-Nitroimidazoles (Part II).

More than 170 1-methyl-5-nitroimidazoles substituted in the 2-position via an aminomethyl, thiomethyl, sulphinylmethyl or sulphonylmethyl group were synthesized and tested for their effect against various protozoa. In the NMRI mouse which had been i.p. infected with Trichomonas fetus 2 compounds showed an effect superior to that of tinidazole and 31 showed similarly good efficacy as that compound. In comparison with metronidazole 54 preparations proved to be distinctly more active, while 34 others lay in the range of efficacy of the standard compound. A large majority of the most active derivatives is substituted in the 2-position via a C--S bridge with heterocyclics, particularly with a pyridyl radical. An effect against Entamoeba histolytica in the intrahepatically infected golden hamster was observed much less often. Only 14 preparations developed a systemic effect comparable with that of metronidazole. In the NMRI mouse infected i.p. with Trypanosoma brucei or s.c. with T. cruzi parasitemia was clearly influenced by 11 compounds. With a few exceptions a trypanocidal effect against T. brucei occurred only at high doses. Only 3 compounds showed pronounced suppressive activity against blood forms of T. cruzi and only after prolonged treatment. The structure-activity relationship of the new 5-nitroimidazoles is discussed.

Animals↗
PubMed1978

Chemotherapeutically active nitro-derivatives. 4. 5-Nitroimidazoles (Part IV).

16 novel 1-methyl-5-nitroimidazoles substituted at 2-position were examined for activity against various protozoa, in particular trichomonads in NMRI mice and amebae in golden hamsters. Six of the compounds proved to be superior to metronidazole and one superior to tinidazole against trichomonads. The compounds exhibited no marked effect against amebae and trypanosomes. The structure-activity relationships of the new compounds are discussed.

Amebiasis↗
PubMed1977

Structural changes on Entamoeba histolytica trophozoites after cryopreservation in liquid nitrogen.

Trophozoites of Entamoeba histolytica cultures which had been deep-frozen in the presence of 5% DMSO, along with untreated cells and cells treated with DMSO (5%), were examined for fine-structural changes. After deep-freezing in liquid nitrogen only a few amoebae exhibited normal nuclear and cytoplasmic structure. One frequently observed but unspecific finding pertaining to recovered cells is the separation of the cytoplasm into large vacuolated (coarse-granular) and electron-optically fine-granular (hyaline) zones. The glycogen which normally lies in the cytoplasm is always eluted. In many cases numerous short RNP helices are scattered unevenly in the vesicular plasma, but they are also found in larger masses adjacent to the membranes of still intact and already damaged nuclei. Moderately damaged nuclei have a poorly folded membrane and their chromatin is markedly denatured. More heavily damaged nuclei have a membrane which has partly fibrillated or ruptured and then formed conspicuous folds, where the nuclear membrane has ruptured nucleoplasmic remnants of chromatin and button-like bodies appear to pour into the surrounding cytoplasm. The final destruction of the cell is marked by coalescing autolytic zones, first in the vacuolated and later in the fine-granular cytoplasm. Finally only remnants of the nuclear membrane and of the membranes of numerous vacuoles remain. It is assumed that most of the changes in the cytoplasm are of a secondary nature and are caused by the early functional disturbance of the nucleus.

Animals↗
PubMed1977

Survival of Aegyptianella pullorum, Anaplasma marginale and various parasitic protozoa following prolonged storage in liquid nitrogen.

Various protozoa species were examined using in vivo and in vitro methods to determine their ability to survive prolonged periods of storage in liquid nitrogen. The following protozoan species were successfully recovered after they had been cryopreserved for a period over 10 years: Trypanosoma lewisi, T. cruzi, T. congolense, T. brucei, T. rhodesiense, T. gambiense, T. evansi, T. equinum, T. equiperdum, Leishmania donovani, Plasmodium berghei, P. praecox (relictum), Babesia rodhaini and B. canis. The longest survival period that has been successfully tested so far is between 5 and 7 years for Eimeria species, for monoxenically (A--C) and axenically grown E. histolytica cultures between 2 and 7 years and trichomonades, including Crithidia sp., between 6 and 8 years. Aegyptianella pullorum was successfully recovered after 6.97 years and Anaplasma marginale after 1.92 years. The freezing techniques are briefly described.

Animals↗
PubMed1977

1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine, a new drug with marked activity against Entamoeba histolytica. Short communication.

1,4-Bis-[1-methyl-5-nitroimidazolyl-(2-methyleneimino)]-piperazine (HOE 316) administered orally produces an effect which is clearly superior to that of metronidazole against Entamoeba histolytica in the golden hamster and slightly inferior against Trichomonas fetus and T. vaginalis in the mouse. The acute tolerance of the compound is very good (LD 50% greater than 10 g/kg body weight). It is assumed that the possible main metabolite of HOE 316 is a monohydrazone: 1-methyl-2-(4-amino-piperazino-1-imino-methyl)-5-nitroimidazole.

Animals↗
PubMed1977

Chemotherapeutically active nitro compounds. 4. 5-Nitroimidazoles (Part I).

More than 135 new 2-methyl-5-nitroimidazoles substituted in 1-position and 1-methyl-5-nitroimidazoles substituted in 2-position were investigated for their activity against various protozoan species, in particular Entamoeba histolytica in the golden hamster, Trichomonas fetus, Trypanosoma brucei and T. cruzi in the NMRI mouse. Among the nitroimidazoles substituted in the 1-position only two preparations exhibited a similar effect as metronidazole preparations exhibited a similar effect as metronidazole against T. fetus. In the class of the nitroimidazoles substituted in the 2-position 16 compounds were as effective as metronidazole, 19 showed an effect superior to metronidazole, 1 was as good as tinidazole and 2 exhibited an activity superior to tinidazole against T. fetus. Only few compounds displayed any amoebicidal activity. Of the mono and bis-hydrazones of 1-methyl-5-nitroimidazole-2-aldehyde substituted in the 2-position 3 compounds had an amoebicidal effect 2 to 8 times stronger than that of metronidazole. Only few representatives of the 1-methyl-5-nitroimidazoles substituted in the 2-position produced a useful trypanocidal effect when given in relatively high doses. The structure-activity relationship of 5-nitroimidazole derivatives has been discussed.

Animals↗
PubMed1977

[Chemotherapeutically effective nitro compounds. 3rd communication: nitropyridines, nitroimidazopyridines and related compounds (author's transl)].

New 2-nitropyridines and 3-nitropyridines, and 3-nitroimidazo-[1,2-a]-pyridines and related compounds (together 106) were synthesized and tested for their chemotherapeutic efficacy against trichomonads, amoebas and other organisms, such as Eimeria tenella, bacteria, fungi, helminths. Several 2-nitropyridines revelaed a detectable systemic effect against Entamoeba histolytica (extraintestinal amoebiasis of the golden hamster) and also a weak activity against Trichomonas fetus in the NMRI-mouse. Only a few 3-nitropyridines showed a marked systemic effect against trichomonads. Of the 3-nitroimidazo-[1,2-a]-pyridines, only the electroneutral carboxylic acid amide group exhibited a pronounced activity, exclusively against trichomonads; however, the activity was nullified again by electronegative, electropositive and other electroneutral substituents. As they were not superior in chemotherapeutic respect compared to the known standard preparation (metronidazole), no further tests were carried out with the most effective compounds.

Amebicides↗
PubMed1976

[Chemotherapeutically active nitro compounds. 2nd communication: Nitrodiphenyl sulfones (author's transl)].

A number of new 4-nitro-4'-amino-diphenyl sulfones and related compounds were prepared and investigated as to their therapeutic activity. They showed a good systemic activity against tubercle bacilli (M. bovis, NMRI mouse) and plasmodia (P. berghei, NMRI mouse). The test results reveal that the 4-nitro-4'-amino-diphenyl sulfones possess a spectrum of activity similar to that of diamino-diphenyl sulfone (DDS). It is assumed that 4-nitro-4'-amino-diphenyl sulfones in vivo are converted into DDS derivatives by reduction. The advantages of the new compounds, however, were too insignificant as compared to DDS to justify further extensive trials.

Animals↗
PubMed1976

Trypanocidal effect of diamidine 98/202 in experimental Trypanosoma rhodesiense infection of the stumptailed macaque (Macaca arctoides).

The trypanocidal effect of preparation 98/202, a 6-Amidino-2-(4'-amidinophenyl)-thionaphthene dilactate, was investigated in 4 stumptailed macaques (Macaca arctoides) infected with Trypanosoma rhodesiense (strain: Hamburg, 1962), of which 2 animals had been treated previously with diminazene and pentamidine, respectively. The curative treatment with preparation 98/202 was carried out in all cases in the late stage of infection; at the beginning of treatment 3 of the 4 animals had already shown malaise with distinct affection of the central nervous system. The individual dose was 5 mg/kg (base) and was given by deep intramuscular injection on 2, 3 or 4 consecutive days. During the trial period elimination of the parasites from the blood was observed in all monkeys, and in 3 out of 4 animals also in the liquor cerebrospinalis. In one animal a parasitological cure could be demonstrated. Two animals died as a result of the very advanced infection, one animal had to be killed prematurely because of numerous deep skin necroses without healing tendency. In 2 animals previously treated with diminazene and pentamidine, respectively, the T. rhodesiense strain developed a distinct resistance to pentamidine, diminazene and preparation 98/202. The resistance induced with pentamidine against diminazene and preparation 98/202, however, was only transitory and disappeared after withdrawal of the preparation. A brief description of the course of infection is given and possible sites of action of preparation 98/202 are discussed.

Amidines↗
PubMed1975

[Chemotherapeutic effects of nitro compounds. 1. Nitroanilines].

More than 200 nitro compounds, most of them nitroaniline derivatives substituted with one or more radicals having a basic reaction, were prepared and investigated as to their therapeutic activity against bacteria, fungi, protozoa, helminths, viruses and tumors. Several mono-nitrobenzenes with a radical having a basic reaction showed weak in-vitro activity against gram-positive bacteria and against Crocker's sarcoma 180; they also showed systemic activity against nematodes (Aspiculuris tetraptera) and viruses. The majority of therapeutically active compounds with pronounced in-vivo activity against Trichomonas fetus, Entamoeba histolytica, Schistosoma mansoni, cestodes, nematodes (Ancylostoma caninum), viruses (influenza, MHV, SAV and EMC) and various types of carcinoma (Ehrlich's carcinoma, leukemia 1210, Crocker's sarcoma 180) were dinitrobenzene derivatives with one radical having a basic reaction and electropositive groups or unreactive or reactive chlorine atom, and di-nitrobenzene with two equal or two different radicals having a basic reaction. Compound No. 70 revealed a marked in-vitro activity against fungi (Trichophyton; Microsporum, Candida albicans). Other nitro compounds such as bis-mono- and bis-dinitrobenzene derivatives likewise showed a systemic action against E. histolytica, viruses and, in particular, carcinoma (Crocker's sarcoma 180, Ridgway's osteosarcoma). Oxygen and sulfur analogue compounds as well as compounds produced by reduction also possessed a distinct activity against E. histolytica and viruses. On the basis of the present results particularly the dinitrobenzenes substituted with two radicals having a basic reaction include a number which have in common that a structure/activity relationship is recognizable in respect of E. histolytica, Schistosoma mansoni and different types of viruses. The activity against viruses in this class of compounds is probably due to an increased interferon production in the host animal. Whether the mechanism of action is the same against E. histolytica or Schistosoma mansoni has not been determined so far. A tumorigenic effect was observed mainly in those di-nitrobenzenes which are classed as alkylating compounds. Because of the small chemotherapeutic index the trials were not continued with the most effective compounds mentioned.

Aniline Compounds↗