Search PubMed⌕ Search

Biomedical subjects

E Chenu

Publications and source records attributed to E Chenu.

At least 37 records · Page 2Linked to original sources
PubMed1989

Synthesis and evaluation of antileukemic activity of 5-thienyl- or 5-(2-furyl)-2,3-dihydro-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(alkylcarbamates) and derivatives.

Treatment of N-(2-furoyl)proline or N-thenoylprolines and N-(2-thenoyl)thiazolidine-4-carboxylic acid with acetic anhydride and dimethyl acetylenedicarboxylate gave 5-substituted derivatives of dimethyl 2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate and derivatives of dimethyl 5-(2-thienyl)pyrrolo[1,2-c]thiazole. Reduction of 2 with lithium aluminum hydride gave the diols 3a, 3b, 3c and 3d. These diols yielded the corresponding diacetates 4 by treatment with acetic anhydride. The bis(methylcarbamates) 5a, 5b, 5c, and 5d and bis(isopropylcarbamates) 6b and 6c are obtained with the appropriate isocyanates. The 1-substituted pyrrolizines were synthesized, the 1-acetoxy compounds 7b and 7c further transformed into 1-hydroxy and 1-oxo analogues. The action of hydrochloric acid on 1-acetoxy derivatives gave 3H-pyrrolizines. Evaluation of antileukemic activity was investigated on the leukemia L1210 in vivo, on several bis(alkylcarbamates). The compounds 5c and 5d show good antileukemic activity comparable with the mitomycin.

Animals↗
PubMed1986

Cytostatic action of two nitrosoureas derived from cysteamine.

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG-Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2-[3-(2-chloroethyl) 3-nitrosoureido]D-glucopyranose (CZT), (chloro-2-ethyl)-1(ribofuranosyl-isopropylidene-2'-3' paranitrobenzoate-5')-3 nitrosourea (RFCNU), and (chloro-2-ethyl)-1 (ribopyranosyl triacetate-2'-3'-4')-3 nitrosourea (RPCNU). A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first-pass metabolism leading to the formation of four main plasma metabolites. These metabolites are water-soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups. Experimental screening was performed with these chemically synthesized metabolites. Both N'-(2-chloroethyl)-N-[2-(methylsulphinyl)ethyl]-N'-nitrosourea (CMSOEN2) and N'-(2-chloroethyl)-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition,the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26. 6 Haematological toxicity of both active metabolites is lower than that of CNCC, particularly on platelets which is the main toxicity location due to nitrosoureas.

Animals↗
PubMed1985

Antitumor activity of l-OHP in mice.

The isomeric mixtures of platinum complexes of diaminocyclohexane (DACH) had been found active on several murine tumors. A recent separation of the oxalato-platinum complex of trans-l-DACH isomer allowed more precise screening studies and permitted the selection of one compound: l-OHP was submitted to our murine tumor screening system. The drug was given: (a) at doses of 1-12 mg/kg i.p. or i.v. on day 1, 5 and 9 compared to identical doses of cis-dichlorodiamine platinum II (CDDP) in L1210 bearing mice and (b) to AkR leukemia, LGC lymphoma, glioma 26, B16 melanoma, MA 16-C mammary carcinoma and Lewis lung carcinoma bearing mice at 2 dosages: 5 mg/kg (minimal effective dose on L1210), and 8 mg/kg (subtoxic dose in L1210). Acute LD10 and LD50 appeared similar to CDDP and l-OHP. l-OHP administered i.p. was more active on L1210 than CDDP. On L1210 grafted intracerebrally and on LGC lymphoma l-OHP increased significantly the lifespan while CDDP was inactive. On AkR leukemia, both drugs were active but l-OHP was less toxic. Both drugs were inactive on murine solid tumors. No renal toxicity was observed with l-OHP as compared to CDDP.

Animals↗
PubMed1985

Comparison of the experimental antitumor activities of three nitrosourea derivatives chlorozotocin, RFCNU and CNCC encapsulated in liposomes with those in the free state.

L1210 leukemia was used to compare the antitumor activities of three nitrosoureas (chlorozotocin, RFCNU and CNCC) encapsulated in liposomes with those in the free state. The results obtained varied according to the chemical structure of the compound, its solubility in oil or water, the route of administration into the body, and the treatment dose. The application of liposomes in the chemotherapy of malignant disease deserves further investigations.

Animals↗
PubMed1984

Effects of B16 melanoma transplantation on the respiration of grouped C57Bl female mice.

Two batches of 110 females C57Bl mice were grafted with B 16 melanoma, the first batch at the age of 67 days, the second at 82 days. The animals were divided into groups of 10, and kept under a LD 12 : 12 regimen. The growth of the tumors was more rapid in the second batch. This was accompanied in this batch, by a decrease in body growth, a diminution of heart rate and an increase in QRSII amplitude. Significant decreases in carbon dioxide emission (VCO2) level, mostly during the dark period of time, when the mice had their greatest activity, and decrease in respiratory photic variations at light transitions were obtained when the tumors were well developed. Harmonic analysis of the continuous recording of carbon dioxide shows slight changes in VCO2 ultradian (40 minutes less than tau less than 12 hours) rhythms. The effects on respiration were confirmed by different survival rates and rectal temperatures between tumor grafted and controls submitted to an acute nitrogen normobaric hypoxia.

Animals↗
PubMed1981

Experimental in vivo cross-resistance of vinca alkaloid drugs.

In human therapy, an absence of cross-resistance has been observed between vincristine and vindesine in patients receiving polychemotherapy whilst, in our experimental in vivo studies, such a cross-resistance has been found between Vinca alkaloids. Further studies are required to explain this discrepancy.

Animals↗
PubMed1978

[Azotized emetine analogues: synthesis and evaluation of the anti-amebic and anti-tumoral action of aza-3 emetine and attempted synthesis of aza-2 emetine].

The synthesis of the N,N-bis-(acetylhomoveratrylamido)-1-hydroxymethyl and 1-carboxypropylamines (III a) and (III b) is described. Until now, these molecules could not been cyclized to the corresponding isoquinoline compounds. An attempted synthesis of 3-azaemetine by condensing homoveratrylamine with acetonedicarboxylic acid or its esters did not yield the expected diamide (XIV). However, by subjecting 1,3-bis-(1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolyl)acetone (XV) to a reducing aminoalkylation, one obtained the corresponding ethylamino derivative (XVI) which could be cyclized through Mannich reaction to give 3-azaemetine. The pharmacological screening showed 3-azaemetine to be less toxic than emetine in the mouse and without antiamebic and antitumor activity against P 388 Leukaemia in the mouse (25).

Amebicides↗
PubMed1978

Oncostatic effects of Alangium vitiense extracts (ICIG-EORTC 1131, 1186 and 1207) on lymphoid murine tumors.

A total alkaloid and two purified alkaloid extracts of Alangium vitiense were found to be oncostatic for L1210 leukemia; the total alkaloid exerted a noticeable activity, and the purified extracts exerted a borderline activity. These two purified extracts are noticeably oncostatic for two other lymphoid neoplasias in mice, P388 leukemia and Gardner lymphosarcoma. These compounds are not active on Warner myelomonocytic leukemia WEH13 or on B16 melanoma.

Alkaloids↗
PubMed1975

The oncostatic and immunosuppressive action of new nitrosourea derivatives containing sugar radicals.

Four new nitrosourea derivatives represent an appreciable progress in the treatment and cure of L1210 leukemia. Their therapeutic index is higher than that of CCNU and MeCCNU. Of these compounds, RFCNU may prove the most promising, as its therapeutic index is the highest of those for all the four compounds studied; moreover, unlike the other products, it is not immunosuppressive, whether administered before or after the antigen.

Animals↗