Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hycanthone”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1976

Influence of hycanthone on morphology and serotonin uptake of Schistosome mansoni.

The intrinsic content of serotonin (5HT) and the uptake of 5HT by Schistosoma mansoni taken from mice which were given a single intramuscular therapeutic dose of hycanthone were studied. Drug-exposed worms were found to have intrinsic values of 5HT which were similar or slightly less than controls. Uptake measurements were made on single and on paired worms recovered from mesenteric, portal, or hepatic sites and incubated in 75% horse serum or in Fischer's medium. All groups of treated worms were found to take up, on average, similar or lower amounts of 5HT compared to controls. These findings are in contrast to a recent report of very considerable increases in content or in 5HT acquisition in vitro by hycanthone-exposed parasites. This communication suggests that the mode of action of hycanthone cannot be explained as being due to increased 5HT uptake. Morphological changes in hycanthone-treated worms include loss of body weight and size, loss of hemoglobin pigment from the gut, deterioration of the tegument, and derangement of the vitellaria. The loss of gut contents occurs early after exposure to hycanthone and may indicate that interference with gut physiology and the nutritional state of the worms is one consequence of the drug, although the mechanism of these changes has not yet been elucidated.

Animals↗
PubMed1980

A study of the mode of action of hycanthone against Schistosoma mansoni in vivo and in vitro.

Schistosomes obtained by perfusion from host animals as early as 2 hours after in vivo treatment with hycanthone and transferred into untreated recipient hamsters died in the recipient host. In contrast, unexposed schistosomes transferred into recipient hamsters treated from 7 days to 36 hours previously showed a normal survival. In vitro treatment of schistosomes with hycanthone concentrations comparable to those used in in vivo studies, followed by transfer of the parasites into normal hamsters, resulted in death of the worms. The time of lethal hycanthone exposure in vitro could be as short as 15 minutes. Hycanthone-resistant schistosomes or immature worms were not affected under similar in vitro conditions. Our data suggest that the schistosomicidal effect of hycanthone is not caused by a host-derived metabolite.

Animals↗
PubMed1976

Histological study of the effects of hycanthone on the frog's ventricle in the presence of a soluble sodium salt of prednisolone hemisuccinate.

The histological picture of the ventricle of frog's heart exposed to the action of Hycanthone in Ringer's solution in concentration of 1:1 was compared with that of the ventricle of frog's heart exposed to Ringer's solution devoid of the drug and with that of frog's heart exposed to Ringer's solution containing Hycanthone in concentration of 1:1 in addition to a soluble sodium salt of prednisolone hemisuccinate in concentration 1:1. It was found that the structure of the ventricle of the heart exposed to the action of Hycanthone in the presence of the soluble sodium salt of prednisolone hemisuccinate was close in pattern to the structure of the ventricle of the heart exposed to Ringer's solution alone, while the ventricle of the heart exposed to Hycanthone alone in Ringer's solution in concentration of 1:1 was different in that the muscle fibres swollen, the cytoplasm was paler with less marked striations, the nuclei were swollen and paler, the epicardial cells were swollen and the connective tissue pattern was distorted. This denoted that the morphological changes that occurred in response to Hycanthone in the presence of the soluble sodium salt of prednisolone hemisuccinate was less marked than those which occurred in its absence.

Animals↗
PubMed1976

The effects of dyphylline [7-(2,3-dihydroxypropyl) theophylline] on the toxicity of hycanthone on the frog's heart.

The effects of the topical application of Dyphylline in concentrations of 1.0 mg/1.0 ml and 10 mg/1.0 ml Ringer's solution and 25 mg/1.0 ml, 0.065% NaCl solution (the content of ampoules in clinical use) were investigated on frog's heart in situ. Dyphylline in all of the above concentrations had a stimulatory effect on the frog's heart. Hycanthone methanesulphonate in concentration of 1.0 ml/1.0 ml when topically applied to the frog's heart had a depressant effect on both of the contractility and rhythmicity. The depressant effects of Hycanthone in concentration of 1:1 were compared before and after the topical application of Dyphylline in the above mentioned concentrations. It was found that Dyphylline in concentration of 1.0 mg/1.0 ml could partially antagonize the depressant effect of Hycanthone on the heart rate but not on the force of contraction. Dyphylline in concentration of 10 mg/1.0 ml could partially antagonize the depressant effects of Hycanthone on both of the heart rate and the force of contraction. Dyphylline in concentration of 25 mg/1.0 ml could completely antagonize the depressant effects of hycanthone on both of the heart rate and the force of contraction.

Animals↗
PubMedDate not supplied

Reversing multidrug resistance in L1210 tumor cells by hycanthone or chlorophenoxamine in vitro and in vivo.

In the presence study we demonstrated that hycanthone and chlorophenoxamine can modulate the resistance of multidrug resistant (MDR) murine L1210 leukemia tumor lines in vitro and in vivo. The circumvention of MDR by hycanthone and chlorophenoxamine in vitro was demonstrated by a short-term test using tritiated nucleic acid precursors and by flow cytometrical measurement of accumulation of rhodamine 123. Furthermore, we treated mice bearing resistant L1210 ascites cells with doxorubicin and hycanthone or chlorophenoxamine. Hycanthone in combination with doxorubicin significantly inhibited tumor growth. We also found an improved therapeutic effect of doxorubicin plus chlorophenoxamine. Our results in vitro and in vivo indicate that hycanthone and chlorophenoxamine might be appropriate tools for the circumvention of MDR in human tumors.

Animals↗
PubMed1989

Early years of the Salmonella mutagen tester strains: lessons from hycanthone.

The 1960s witnessed detailed studies on the genetic properties of a large number of histidine-requiring mutants of Salmonella typhimurium. The early 1970s saw development of selected strains, the Ames strains, for use in rapid, cheap, sensitive, and manipulable tests of chemicals and chemical mixtures for genotoxic activities. Our contribution during this latter period was an investigation into the mutagenicity of hycanthone and some of its analogues. Some lessons that this study provided are enumerated. Hycanthone is definitely a liver carcinogen in rodents predisposed by hepatic hyperplasia. Between 1969 and 1975, an estimated total of 100 kg of hycanthone was injected into some 1,000,000 humans with liver hyperplasia caused by infections with parasites. It may now be possible to assess directly the long-term impacts of hycanthone in man.

Animals↗
PubMed1990

Inhibition of in vitro RNA synthesis by hycanthone, oxamniquine and praziquantel.

The schistosomicides, hycanthone, oxamniquine and praziquantel, were found to inhibit the in vitro RNA synthesis using isolated hamster liver nuclei. Preincubation of the nuclei with these drugs revealed that the inhibitory effect of oxamniquine was irreversible and progressed with time, whereas that of hycanthone and praziquantel was reversible. On the other hand, hycanthone and praziquantel have a high affinity for DNA but oxamniquine does not. The data indicate that the mechanism of inhibition by oxamniquine is different from that of hycanthone and praziquantel.

Animals↗
PubMed1982

Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents.

Fourteen patients with active schistosomiasis mansoni in spite of previous treatment with oxamniquine and/or hycanthone were treated with praziquantel, single oral dose of 45 to 50 mg/kg body-weight. All underwent clinical, laboratory and electrocardiographic examination before and after treatment. Untoward effects (dizziness, drowziness, nausea and abdominal pain) were observed in ten. Laboratory findings disclosed no significant alteration and the electrocardiograms showed no abnormalities. Monthly follow-up examinations of 13 patients for six consecutive months showed parasitological cure in all. Before praziquantel treatment strains of Schistosoma mansoni were isolated from two patients, one treated three times with oxamniquine and the other with hycanthone once and oxamniquine twice. Progenies of these strains were maintained in Biomphalaria glabrata and mice. Groups of these infected mice were then treated with oxamniquine, hycanthone, niridazole and praziquantel and results compared with the BH strain maintained in our laboratory for many years. Schistosomicidal activity was assessed by the localization of worms in the portal vein system and oogram changes. Progenies from the strains isolated in this study were resistant to oxamniquine and hycanthone but sensitive to niridazole and praziquantel. The BH strain was sensitive to all four drugs. The serial runs of S. mansoni strains through intermediate and definitive hosts have not influenced their reactions to these schistosomicides.

Adolescent↗
PubMed1983

Effect of hycanthone administered in vivo upon the incorporation of radioactive precursors into macromolecules of Schistosoma mansoni.

Mice infected with Schistosoma mansoni were treated with hycanthone or with 8-chloro-2[2-(diethylamino)ethyl]-2H-[1]benzothiopirano-[4,3, 2-cd]-indazole-5-methanesulphonate (IA-4). Schistosomes were obtained by perfusion at various times after drug administration and tested for their ability to incorporate radioactive precursors of DNA, RNA and protein. In adult worms, male or female, the incorporation of radioactive thymidine was severely and irreversibly inhibited after treatment with either drug. Uridine and leucine incorporations were also inhibited, though to a lesser extent. On the contrary, the synthetic activities of immature worms were unaffected by hycanthone and only partially or temporarily depressed by IA-4. Hycanthone-resistant schistosomes, when tested between 1 and 7 days after treatment, showed a pattern of precursor incorporation which was virtually identical to that of untreated worms. These results are consistent with the hypothesis that hycanthone and IA-4 may kill schistosomes by interfering with their nucleic acid synthesis.

Animals↗
PubMedDate not supplied

Effect of praziquantel versus hycanthone on deoxyribonucleic acid content of hepatocytes in murine schistosomiasis mansoni.

Cytophotometric measurement of the effect of praziquantel (500 mg/kg for 2 days) versus hycanthone (60 mg/kg for 3 days) on hepatocyte nuclear deoxyribonucleic acid (DNA) content was evaluated in Schistosoma mansoni infected mice. Drugs were given 8 weeks post-infection and repeated weekly for 4 weeks. DNA values of infected untreated control and infected drug treated groups were related to the median and upper diploid DNA values of normal control. Schistosoma mansoni infection per se did not change the hepatocyte DNA content, yet aneuploidy was 16.7%. Praziquantel did not result in significant change of DNA content or ploidy, while hycanthone resulted in marked significant increase of DNA content (328.9%) and aneuploidy (100%), compared to infected untreated control. Histopathological examination revealed hyperchromatic nuclei with mitosis in the hepatocytes of hycanthone treated mice, but not in praziquantel treated animals. These DNA changes were found to correlate with the reported safety of praziquantel and the carcinogenicity of hycanthone.

Animals↗
PubMed1993

Preferential intercalation at AT sequences in DNA by lucanthone, hycanthone, and indazole analogs. A footprinting study.

DNAase I footprinting has been used to probe the DNA sequence selectivity of the antitumor intercalating agents lucanthone (1), hycanthone (2), 6-chlorolucanthone (7), and four indazole analogs (IA-3-IA-6). The latter have a benzothiopyranoindazole chromophore substituted with a diethylaminoethyl side chain identical to that attached to the thioxanthenone chromophore of compounds 1, 2, and 7. IA-3 and IA-5 are lucanthone analogs bearing a methyl group at position 4, whereas IA-4 and IA-6 are hycanthone analogs bearing a hydroxymethyl group. IA-3 and IA-4 have an additional chloro group at position 6. Studies employing the 160-bp tyrT DNA fragment as substrate to assay inhibition of DNAase I-mediated cleavage show that both lucanthone and hycanthone bind preferentially to AT sites. They discriminate against GC-rich sequences as well as short runs of a single base, which are often cut more readily in the presence of the drugs compared to the control. The indazole analogs exhibit more pronounced selectivity of binding to AT sequences and promote enhanced DNAase I cleavage both at GC-rich sequences and at homooligomeric runs of adenines or thymines. The results of further DNAase I cleavage inhibition assays, performed with three more restriction fragments having different base pair arrangements, are fully consistent with those obtained with the tyrT fragment. They reveal that the preferred binding sequences for lucanthone, hycanthone, and the indazole analogs are predominantly composed of alternating A and T residues.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1975

Clinical evaluation of niridazole and hycanthone in schistosomiasis mansoni endemic areas.

One hundred patients with active schistosomiasis mansoni were treated with niridazole (25 mg/kg/day po for 7 days). The most serious side effects were those connected with the neuropsychic area (convulsion, hallucination, etc.). Therapeutic activity, based on repeated stool examinations, was about 90% in adults and 60% in children. Because of the side effects, as well as the long-term schedule of treatment, niridazole is not recommended for use under field conditions. Seven hundred and forty-five patients were treated with hycanthone (2.5 mg/kg im) after clinical examination. The side effects observed were mild and of short duration (24-48 hr). The therapeutic activity was very high (about 95% cure). So far we have treated more than 9,000 infected patients without severe complications, including hepatic failure and death, which have been reported by some authors. A hycanthone-resistant strain has been isolated from two patients unsuccessfully treated twice with hycanthone and once with niridazole. Considering that an important aspect of the control of schistosomiasis is mass treatment, further studies regarding mutagenicity, teratogenicity, resistance, and toxicological effects of hycanthone are still required before this drug can be recommended for wide use.

Adult↗
PubMed1980

Action of antischistosomal drugs, hycanthone and its analog 1A-4 N-oxide, on viral interferon induction.

Two antischistosomal drugs, hycanthone and its indazole analog 1A-4 N-soxide, of which the former is a potent mutagen, differed markedly in their ability to depress interferon induction by influenza virus in rhesus monkey kidney (LLC-MK2) cell cultures. At the concentration of 10 micron/ml, hycanthone reduced interferon yields as much as 73%; the same quantity of analog had no adverse effect on interferon induction. Pretreatment of cell cultures with the analog negated the inhibitory activity of hycanthone on viral interferon induction; however, this did not occur when the sequence was reversed. Interferon-mediated antiviral cellular resistance was not affected when cell cultures were pretreated with either hycanthone or 1A-4 N-oxide. A possible association may exist between the mutagenicity of antischistosomal drugs and their ability to affect interferon synthesis.

Animals↗
PubMed1976

Long-term hepatocellular effects of hycanthone and of two other anti-Schistosomal drugs in mice infected with Schistosoma mansoni.

In confirmation of an earlier study, it was found that in mice infected with Schistosoma mansoni hepatocellular carcinomas are induced by hycanthone, an antischistosomal drug and potent frameshift mutagen. In addition, a high incidence 1) of micronodular hepatocellular whirling lesions with increased basophilia, 2) of other proliferative areas of altered cellularity and 3) of precancerous nodules was found in the livers of schistosome-infected mice treated with hycanthone. A dosage schedule of hycanthone which was too small to have any significant chemotherapeutic effect in mice (3 X 3 mg/kg) was sufficient to induce a statistically highly significant incidence of micronodular lesions and of precancerous nodules. Hence, the hepatic tissue proved more susceptible to low doses of this drug than the parasite. No significant hepatocarcinogenic effects or other hepatocellular changes were induced by chemotherapeutically effective doses of two related equipotent antischistosomal compounds, a chloroindazole analog of hycanthone, IA-4, and the tetrahydroquinoline derivative, oxamniquine.

Animals↗
PubMed1979

Induction of hepatic neoplastic lesions in mice with a single dose of hycanthone methanesulfonate after partial hepatectomy.

Experiments were designed to determine whether hycanthone methanesulfonate (1-([2-(diethylamino)ethyl]amino)-4-(hydroxymethyl)thioxanthen-9-one monomethanesulfonate), an antischistosomal drug, and its analog, IA-4-N-oxide (8-chloro-2-[2-(diethylamino)ethyl]-2H-[1]benzothiopyrano[4,3,2-cd]indazole 5-methanol monomethanesulfonate), will induce neoplastic lesions in the livers of mice not infected with Schistosoma mansoni. All the mice received a single i.m. injection of hycanthone methanesulfonate (76 mg/kg), IA-4-N-oxide (80 mg/kg), or an equivalent volume of the solvent, 0.9% NaCl solution, 42 hr after partial hepatectomy. Of the mice receiving hycanthone methanesulfonate and living 200 days or longer, hepatocellular carcinoma was seen in 11.5% and liver sarcoma was seen in 4.2%. This type of malignant neoplasm was not seen in the animals receiving either IA-4-N-oxide or 0.9% NaCl solution. In addition, mice receiving hycanthone methanesulfonate showed a significantly higher incidence of both type 1 (43% compared to 21% in controls) and type 2 (21% compared to 12% in controls) hepatocyte neoplasms. Mice receiving IA-4-N-oxide showed no increased incidence of neoplasms.

Animals↗
PubMed1981

Effects of hycanthone and praziquantel on monoamine oxidase and cholinesterases in Schistosoma mansoni.

The effects of hycanthone and praziquantel on the activities of monoamine oxidases and cholinesterases were studied in the 600-g supernatant from homogenates of Schistosoma mansoni and mouse liver or brain. Hycanthone was shown to be a very potent inhibitor of monoamine oxidases from worms and mouse liver. Hycanthone also inhibited the specific and nonspecific cholinesterases of S. mansoni, but cholinesterase from mouse brain was not affected significantly by this drug. Praziquantel showed no effect on monoamine oxidase from mouse liver or the parasite; however, it was slightly inhibitory to S. mansoni cholinesterases at very high concentrations. Mouse brain cholinesterase required an even higher concentration of praziquantel to observe inhibition. The inhibition of monoamine oxidase in S. mansoni by hycanthone adds a new mode of action to our knowledge of this compound, and suggests another possibility for the development of future anthelminthics.

Animals↗
PubMed1977

Effects of hycanthone on neuromuscular systems of Schistoma mansoni.

Hycanthone has a variety of effects on muscular activity and neurotransmitter systems of schistosomes. These include interference with neuronal storage of 5-hydroxytryptamine (5-HT), an increase in the length of schistosomes, a weak stimulation of motor activity, and an inhibition of acetylcholinesterase activity. However, the findings reported in this paper indicate that none of these effects can be related to the mode of the antischistosomal action of hycanthone because (a) these effects are observable only after, but not prior to, the hepatic shift, (b) they are not demonstrable with anti-schistosomal strucutral analogs of hycanthone, or (c) the same effects are elicited in hycanthone-resistant schistosomes. Dansyl choline, under conditions recommended by others, does not stain selectively neuronal structures of schistosomes, but such structures can be visualized under different conditions. However, this stain lacks specificity for cholinergic neurons or receptors because no cholinergic drug can block binding of dansyl choline and because the same fluorescence staining effects are observed with dansic acid and dansyl chloride.

Animals↗
PubMed1995

Molecular analysis of the TK locus in L5178Y large and small colony mouse lymphoma cell mutants induced by hycanthone methanesulfonate.

Mouse lymphoma cells of the L5178Y TK + /-3.7.2C line were exposed to varying concentrations of the anti-schistosomal drug hycanthone methanesulfonate. The trifluorothymidine (TFT)-resistant cells fell into two classes based on colony size. Southern blot analyses were performed using NcoI-digested DNA from a number of large and small mutant colonies from each treatment group. Two different restriction fragment banding patterns were identified in these analyses, those colonies that contained the 6.4 kb NcoI restriction fragment and those that did not. A total of 471 mutant colonies were analyzed and 84.5% (398) of these colonies did not exhibit the 6.4 kb fragment. There did not appear to be a hycanthone methanesulfonate dose response effect in the number of colonies that did not contain the 6.4 kb fragment among the treated groups. In addition, 82% (154 out of 188) of spontaneous mutants did not contain the 6.4 kb fragment. The results imply that greater than 80% of all spontaneous mutations found in the mouse lymphoma assay regardless of colony size do not contain the 6.4 kb fragment and each may be considered to be a large scale mutation. In addition, greater than 80% of the hycanthone induced mutations in the mouse lymphoma assay do not contain the 6.4 kb fragment and thus may be considered to be a large scale mutation.

Animals↗