Ascitic Form Of Ehrlich Carcinoma Research Articles

Design, synthesis and biomedical evaluation of mostotrin, a new water soluble tryptanthrin derivative.

Mostotrin (MT), a novel compound, at least five orders of magnitude more soluble in water than its mother substance, was designed and synthesised from tryptanthrin (TR). Its structure was established by nuclear magnetic resonance and mass spectrometry data and confirmed by X-ray analysis, revealing that MT is a pentacyclic product with an additional pseudo-cycle formed with the participation of one intramolecular hydrogen bond. Antimicrobial activity and cytotoxic action against tumour cells in vitro, as well as anti-tumour effects, acute toxicity and anti-inflammatory activities in vivo, were evaluated. Antimicrobial proper-ties of MT against Mycobacterium spp and Bacillus cereus ATCC 10702 appeared to be the same as that of TR, but against the other strains used it was weaker. Furthermore, MT exhibited 5-10 times higher cytotoxic activities against tumour cell lines HCT-116, MCF-7 and K-562 than TR, but was less toxic than TR (LD50 of MT was 375 mg/kg, while LD50 for TR was 75 mg/kg). Additionally, compounds MT and TR were studied in DNA binding tests. The quenching of its fluorescence on addition to DNA solution established MT to be capable of binding to DNA. Its anti-tumour action in vivo on mice with the ascitic form of Ehrlich carcinoma was promising, particularly with joint application of MT and the antitumour drug doxorubicin. In this model, the survival and life span for the doxorubicin and 1 co-treatment group were significantly higher compared to doxorubicin treatment alone. The compound MT showed a lower immunosuppressive effect than TR at the early stages of inflammation induced in mice by LPS from E. coli (MT hardly inhibited the release of IL-1, IL-2, or INF-γ). These results demonstrated that MT is a perspective hit compound for drug development. In our opinion, further evaluation on the biological effects of MT and its synthetic analogues could lead to safer and more effective anti-tumour and anti-tuberculosis agents than TR itself. MT has also the prospect of application in combination with known anti-tumour drugs for the treatment of oncological diseases.

Antineoplasic Effect of Aqueous Extract of Plectranthus Amboinicus in Ehrlich Ascites Carcinoma

There are 46,000 new cases of peritoneal carcinomatosis per year in the USA and 17,700 in Brazil. New media, including plant derivatives, are being tested in its treatment. Plectranthus amboinicus is a medicinal plant widely used in Brazil, especially in the northeast region, for the treatment of various diseases, including cancer. This present study evaluates the intraperitoneal use of aqueous extracts of Plectranthus amboinicus (AEPa) at a dose of 200 mg / kg for the treatment of the ascitic form of Ehrlich carcinoma. It is concluded also the AEPa produced antineoplastic effect in ascitic form of Ehrlich carcinoma.

Antibiotika aus Basidiomyceten, XV [1]. 1-Hydroxy-2-nonin-4-on, ein antifungischer und cytotoxischer Metabolit aus Ischnoderma benzoinum (Wahl.) Karst. / Antibiotics from Basidiomycetes. XV [1]. 1-Hydroxy-2-nonyn-4-one, an Antifungal and Cytotoxic Metabolite from Ischnoderma benzoinum (Wahl.) Karst.

A new antibiotic, 1 -hydroxy-2-nonyn-4-one (1), has been isolated from submerged cultures of several strains of Ischnoderma benzoinum. The compound exhibits high inhibitory activity against yeasts and filamentous fungi at concentrations of 1-5 μg/ml. DNA, RNA, and protein syntheses in cells of the ascitic form of Ehrlich carcinoma are strongly inhibited by the same concentrations.

Annuithrin, a new biologically active germacranolide from Helianthus annuus

Investigations on growth inhibition in Helianthus annuus led to the isolation of a new sesquiterpene lactone, a germacranolide with an α-methylene-γ-lactone moiety. The structure of this new germacranolide, annuithrin, was elucidated by spectroscopic methods. Its biological activity has been proven by growth inhibition in straight growth tests, antibacterial tests and inhibition of DNA-/RNA-synthesis in cells of the ascitic form of Ehrlich carcinoma.

Deflectins, new antimicrobial azaphilones from Aspergillus deflectus.

Five structurally related, angular azaphilones, the deflectins, were isolated from the mycelia of Aspergillus deflectus. The structures of all compounds have been established. Besides the inhibitory effects on the growth of bacteria and fungi, these compounds showed lytic activity towards bacteria and erythrocytes and cytotoxic activity towards cells of the ascitic form of Ehrlich carcinoma of mice. The inhibitory effects of the deflectins could be reversed by the addition of serum or serum albumin.

Antibiotics from basidiomycetes. XIII. The alliacols A and B from Marasmius alliaceus (Jacq. ex Fr.) Fr.

Two antimicrobial and cytotoxic metabolites were isolated from fermentation broth of Marasmius alliaceus. The structures of the two crystalline antibiotics, alliacols A (6) and B (1) were elucidated by spectroscopic methods and chemical correlation with alliacolide (3). The alliacols show weak antibacterial and antifungal activity. Both antibiotics strongly inhibit DNA synthesis in cells of the ascitic form of Ehrlich carcinoma at concentrations of 2 approximately 5 microgram/ml. Both alliacols A and B react with cysteine to form adducts with strongly reduced biological activities.

Antibiotics from basidiomycetes. X. Scorodonin, a new antibacterial and antifungal metabolite from Marasmius scorodonius (Fr.) Fr.

Scorodonin (1), a novel biologically active metabolite, was isolated from submerged cultures of the mushroom Marasmius scorodonius (FR.) FR. Its structure has been determined by chemical and physical methods. The antibiotic inhibits the growth of bacteria, yeasts, and filamentous fungi. In cells of the ascitic form of EHRLICH carcinoma the incorporation of thymidine and uridine into DNA and RNA is strongly inhibited by scorodonin whereas the incorporation of leucine into protein is not affected.

Tetronic acid derivatives from Aspergillus panamensis. Production, isolation, characterization and biological activity.

When Aspergillus panamensis, CBS 120.45, was grown on a medium with high carbon and low nitrogen content, it was found to produce six antibiotically active metabolites. All compounds were identified as tetronic acid derivatives; three of them were found to be identical with gregatins A, B, and D, previously reported as metabolites of Cephalosporium gregatum. The other three compounds are new. All six compounds show antibacterial activity towards Gram-negative and Gram-positive bacteria. Five of the antibiotics exhibit inhibitory effects on the macromolecular syntheses in cells of the ascitic form of EHRLICH carcinoma (ECA) of mice.

Antibiotics from basidiomycetes. VII. Crinipellin, a new antibiotic from the basidiomycetous fungus Crinipellis stipitaria (Fr.) Pat.

A crystalline antibiotic, which we have named crinipellin, was isolated from submerged cultures of the basidiomycete Crinipellis stipitaria, strain No. 7612. High resolution mass spectrometry yielded the formula C22H28O5. The antibiotic is most active against Gram-positive bacteria, although yeasts and filamentous fungi are affected to a lesser extent. Crinipellin exhibits high in vitro inhibitory activity against the ascitic form of EHRLICH carcinoma. The incorporation of precursors of DNA-, RNA-, and protein syntheses in EHRLICH carcinoma (and in Bacillus brevis) cells was completely inhibited at 5(10) microgram/ml. In Bacillus brevis the inhibition of the incorporation of uridine was found to be due to an interference by crinipellin with the transport of the precursor into the cells.

Metabolic products of microorganisms. 184. On the mode of action of cladosporin.

Cladosporin, a fungal isocoumarin derivative, strongly inhibits the uptake and thereby the incorporation of uracil and leucine into cells of Bacillus brevis and the incorporation of uridine but not leucine into cells of the ascitic form of Ehrlich carcinoma (ECA) of mice. Normal uptake was not restored by removal of the antibiotic. In cells of Escherichia coli A 19-15 (met-) the inhibition of methionine uptake is associated with the cessation of growth. In a methionine-prototrophic revertant from this organism, the uptake of methionine is still inhibited; growth, however, is hardly affected by cladosporin. In vitro no effect on the DNA-dependent RNA polymerase from E. coli and on the RNA polymerase II from wheat germ could be detected. The poly(U)-directed poly(Phe) synthesis was also not inhibited by cladosporin. It is concluded that cladosporin inhibits uptake processes which, for the case of essential nutrients, leads to loss of viability.

Fusariocin C, a new cytotoxic substance produced by Fusarium moniliforme.

A new cytotoxic substance, fusariocin C, was isolated from the culture filtrate of Fasarium moniliforme A-130. Fusariocin C, C27H28O8, forms pale yellow prisms, melting at 242_??_244°C and has an optical rotation of [a]20D-20.6° (c=0.25, CHCl3). The ultraviolet absorption spectrum was observed at 258 and 365nm. It was cytotoxic to HeLa cell culture and leukemia L 1210 cells, and showed some anti-tumor activity in vivo for ascitic form of Ehrlich carcinoma. The LD50 by intraperitoneal in-jection in mice was determined to be 3.97mg/kg. This compound was almost devoid of anti-microbial activity.

Antibiotics from basidiomycetes. IX. Oudemansin, an antifungal antibiotic from Oudemansiella mucida (Schrader ex Fr.) Hoehnel (Agaricales).

From mycelial cultures of Oudemansiella mucida a crystalline optically active antibiotic, oudemansin (2), has been isolated; its structure is closely related to strobilurin A (1). The relative configuration of oudemansin have been determined by X-ray analysis. The antibiotic exhibits strong antifungal properties and inhibits respiration in fungi, cells of the ascitic form of EHRLICH carcinoma, and rat liver mitochondria.

Antibiotics from Basidiomycetes. V merulidial, a new antibiotic from the Basidiomycete Merulius tremellosus Fr.

Merulidial, a new antibiotic, was isolated from the culture fluid of the Basidiomycete Merulius tremellosus Fr., strain No. WQ 568. Merulidial inhibits a variety of bacteria and fungi. In cells of the ascitic form of EHRLICH carcinoma, DNA synthesis is inhibited at lower concentration as compared to RNA and protein synthesis. Merulidial shows mutagenicity when incubated with the his-mutant TA 100 for Salmonella typhimurium (B.N.AMES). The molecular formula as determined by high resolution mass spectrometry is C15H20O3.

The strobilurins--new antifungal antibiotics from the basidiomycete Strobilurus tenacellus.

The strobilurins are two antifungal antibiotics which were isolated from the mycelium of Strobilurus tenacellus strain No. 21602. The strobilurins A and B are highly active against yeasts and filamentous fungi. In vitro antitumor activity was tested using cells of the ascitic form of EHRLICH carcinoma. The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA). The molecular formulas as determined by high resolution mass spectrometry are C16H18O3 for strobilurin A and C17H19C1O4 for strobilurin B.

Effects of cupric ions on the antitumor activity of diazo-acetyl-glycine derivatives on the solid form of sarcoma 180 in mice

The antitumor activity of diazoacetylglycine derivatives on the ascitic form of Ehrlich carcinoma has been reported to be affected by the simultaneous administration of cupric ions, which caused, for one of the tested compounds (DGI) a sharp increase of its therapeutic efficacy. When tested against the solid form of Sarcoma 180, the association of cupric chloride with diazoacetyl glycine derivatives, causes an increase in the activity for DGI, while no alteration of the activity of DGA and DGE is observed. These results indicate that this potentiation occurs also for a solid tumour which requires systemic absorption and distribution of the drugs. Further investigation is required to study the effects of other treatment schedules, with different timing and relative dosages of administration for the diazo compounds and the copper salt, in order to ascertain the optimal activity obtainable.

Antitumour activity of equinatoxin

Equinatoxin, a highly basic protein extracted from Actinia equina, causes an increase in the survival time of mice bearing the ascitic form of Ehrlich carcinoma, whereas it has no effect on L1210 leukaemia. When tested for in vitro cytotoxicity. by the dye exclusion test, it shows a potent activity on both tumour cell lines, with ED 50 of a few ng/ml. Higher concentrations produce an extensive lysis of the cells. The cytotoxic effects of Equinatoxin are inhibited by phospholipids, thus suggesting that its mechanism of action may be related to interactions with lipids or other charged components of cell membrane. The observed lack of in vivo activity against L1210 leukaemia presumably is due to poor systemic absorption of the protein and/or neutralization by serum factors.

Antineoplastic activity of two new diazoacetyl—glycine derivatives

Two derivatives of diazoacetyl-glycine amide (DGA), N-methyl-DGA (DGMA) and N-ethyl-DGA (DGEA), have been synthesized and tested for their antitumoral activity on the ascitic form of Ehrlich carcinoma. No significant difference was found between the two derivatives and DGA either for their toxicity or for their inhibiting activity on tumor growth. Only at the highest dose used DGMA showed a T/C ratio lower than that of DGA and DGEA, and produced the smallest decrease in the weight of the spleen in tumor-bearing mice.

Tumor-inhibitory effects of combinations of the vinca alkaloids with actinomycin D

Combinations of vinblastine and actinomycin D exhibited synergistic tumor-inhibitory activity against the ascitic form of Ehrlich carcinoma and sarcoma-180 when given daily to mice by intraperitoneal injection for 6 to 10 days. Against L1210 ascites tumor the combination produced approximately additive increases in survival time. Single large doses of vinblastine were much less effective than chronic treatment. Antitumor effects of combinations of single doses of vinblastine and actinomycin D were not significantly greater than those produced by actinomycin D alone, unless the drugs were administered in a sequence, 24 hr apart, initiated with vinblastine. Vincristine was not a very effective inhibitor of the three tumors examined, and in combination with actinomycin D, showed additive or subadditive effects against L1210 and sarcoma-180 ascites tumors. Biochemical studies using the Ehrlich ascites carcinoma indicated that therapy with vinblastine produced an increase in cell size coupled with elevation of the cellular contents of DNA, RNA, and protein. Super-imposition of actinomycin D did not affect the increases in protein or cell size, but largely prevented the increase in DNA per cell and reduced the level of RNA. Incorporation of 3H-uridine into RNA was depressed by treatment with actinomycin D; further reduction in the uptake of isotope by superimposing single doses of vinblastine was achieved only if treatment with the vinca alkaloid preceded actinomycin therapy by 24 hr.

Fixation of radioactive colchicine by Ehrlich ascites carcinoma cells.

IN this communication we wish to report briefly some results on the fixation of radioactive colchicine by the cells of the ascitic form of Ehrlich carcinoma, which is one of a number of tumours used by us in our work with radioactive colchicine.