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Biomedical subjects

J C Chermann

Publications and source records attributed to J C Chermann.

At least 163 records · Page 9Linked to original sources
PubMed1983

Correlation between structure of polyoxotungstates and their inhibitory activity on polymerases.

The 21-tungsto-9-antimonate (TA, HPA 23), a polyoxotungstate, has shown a significant antiviral activity in vivo and in vitro. It inhibits viral and bacterial DNA polymerases. In this paper, several compounds of two polyoxotungstic families, tungstoantimonates and tungstoarsenates, have been used to specify the mechanism of polymerase inhibition. It has been demonstrated that the inhibitory activity of polyoxotungstates is not related to the occupation of their coordinates sites by cations, nor to the nature of these bound cations. Kinetic studies and binding assays have shown that polyoxotungstates bind to the polymerases in competition with the nucleic acid template. This result seems to be related to their polyanionic nature. Furthermore, the size and charge of these compounds may play a prominent part in their affinity for the polymerases.

Antimony↗
PubMed1983

Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).

A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antitumor amino-substituted pyrido[3',4':4,5]pyrrolo[2,3-g]isoquinolines and pyrido[4,3-b]carbazole derivatives: synthesis and evaluation of compounds resulting from new side chain and heterocycle modifications.

New modifications of 10-[[3-(diethylamino)propyl]amino]-6-methyl-5H-pyrido[3',4':4,5]pyrrolo[2,3-g]i sisoquinoline (1b) and 1-[[3-(diethylamino)propyl]amino]-9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carba zole (4b), which display important antitumor properties, were performed either on the side chain or on the intercalating heterocycle. Side chains were introduced by direct substitution of the corresponding chloro derivatives and 6-N-methyl-9-hydroxypyrido[4,3-b]carbazoles analogues were prepared via 9-O-benzoyl-1-chloroellipticines. Evaluation of all new compounds shows no significant increase of in vitro cytotoxicity and percent ILS on the L1210 leukemia system by comparison with the model compounds 1b and 4b.

Animals↗
PubMed1981

2-l-Rhamnopyranosyl[1,2,4]triazolo[1,5-a]pyridine. 4' and 3' Oxidation products. Synthesis and structure-activity relationships.

A series of 2-alpha-L-rhamnopyranosylnitro[1,2,4]triazolo[1,5-a] pyridine C-nucleosides was synthesized from the condensation oa thioiminoether with nitro-2-pyridylhydrazines. Catalytic reduction afforded the corresponding amino derivative. A 1',2' unsaturated C-nucleoside was also obtained by two different routes. Selective oxidation gave the 3'- and 4'-ketonucleosides. The cytotoxic properties of the nucleosides, as well as their effect on viral transformation and replication, were described. The nitro derivatives inhibit viral replication, but at toxic doses; the introduction of a keto function leads to a product which inhibits the replication of murine leukemia virus (MuLV) at noncytotoxic concentrations. The amino derivatives have no significant antiviral effect.

Antiviral Agents↗
PubMed1981

In vivo effect of a new mineral condensed ion (HPA 39) on murine Friend leukaemia.

HPA 39 is a tungsto-antimoniate compound, closely related to the mineral consensed ion HPA 23, from which it differs only by the presence of a potassium instead of a sodium ion inside the central cage. A single parenteral injection of HPA 39 on the same day as virus inoculation decreased the splenomegaly induced by Friend virus in DBA/2 mice and protected 90% of the infected animals against leukaemia. It also lowered the virus content in spleen extracts compared to untreated animals. The efficiency of treatment with HPA 39 on leukaemic mice at a late stage of the disease suggested that the compound may act at the cellular level as well as by inducing virus growth inhibition. HPA 39 also induced an early decrease of peripheral blood reticulocytes, and of the most differentiated erythroblasts in the bone marrow 1 day after injection of the compound. Mineral condensed ions therefore appear to have multiple biological effects both in vitro and in vivo.

Animals↗
PubMed1980

Structure-activity relationships in a series of newly synthesized 1-amino-substituted ellipticine derivatives.

The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor properties toward the L1210 leukemia system are described. No correlation between the apparent association constant to DNA and the in vitro cytotoxicity or the in vito antitumor efficiency could be observed in this series. 9-Hydroxylated derivatives were more cytotoxic in vitro than the corresponding 9-methoxylated compounds. However, their antitumor efficiencies on the in vivo experimental systems do not confirm the advantage of demethylation. The presence of a [(dialkylamino)alkyl]amino side chain at the 1 position of ellipticines increases the antitumor potency: 1-[[3-(diethylamino)propyl]amino]-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (5) is a very potent antitumor compound (% ILS of 134 on the L1210 leukemia system).

Alkaloids↗
PubMed1980

Antitumoral activity of dipyrido [4,3-b] [3,4-f] indoles on L 1210 leukemia.

Newly synthesized dipyrido [4,3-b] [3,4-f] indole compounds have a structural similarity with the DNA intercalating agents ellipticines (pyrido-carbazoles). The procedure of synthesis of these compounds allows the addition of a lateral chain in position 1 of the nucleus. Comparison is made between different substitutions and the resulting cytotoxic and antitumoral effects. The most active compound of the serie (1-gamma-diethyl amino propyl amino)-5-methyl-dipyrido [4,3-b] [3,4-f] indole (called here BD40) protects mice against L1210 leukemia. At the non-toxic dose of 20 mg/kg, particularly, a single infection of this compound given one day after inoculation of 10(5) L1210 cells resulted in an increased life span of 69 per cent with one survivor at 60 days. A combination of cyclophosphamide and BD40 had a synergic effect on the life span of L1210 inoculated mice. The antitumoral action of these drugs may be linked to their intercalative action upon biding to DNA.

Animals↗
PubMed1979

Enhancement of retrovirus production by anti-interferon serum.

In order to investigate the role of endogenous interferon in retrovirus production by infected or induced cells, the effect of two sera raised against mouse interferon has been tested on various C-type murine viruses. Addition of a highly potent anti-interferon serum to 3T3/IC cells chronically infected by the Moloney strain of MLV results in a considerable increase of virus production, as tested by reverse transcriptase assay. This effect is neutralized by an excess of exogenous interferon. The greatest effect of anti-interferon sera was obtained in the derepression of endogenous retroviruses: in K. BALB/c cells treated by IUDR, anti-interferon serum increases up to 50-fold the expression of the endogenous virus. The extinction of virus production which secondarily occurs after its induction by IUdR is likely to be caused by cellular endogenous interferon. The biological parameters of the viral agent produced in the presence of anti-interferon serum are those of the xenotropic endogenous virus.

Animals↗
PubMed1978

Inhibition of rabies virus in vitro by the ammonium-5-tungsto-2-antimoniate.

In vitro multiplication of rabies virus was inhibited by a condensed mineral ion, ammonium-5-tungsto-2-antimoniate (HPA 23). The inhibitory effect was evaluated by two different methods, plaque reduction and one step virus growth. Plaquing showed 50% inhibition with 4.5 microgram/ml of HPA 23 and complete inhibition with 12.5 microgram/ml. A reduction of two logs in virus yield was obtained in BHK21C13S cells in suspension treated with 50 microgram/ml of HPA 23. Inhibition also occurred when treatment with HPA 23 was started 18 to 24 h after infection in the plaque assay but no effect was seen when HPA 23 was added 48 h after virus inoculation. All these inhibitory effects of HPA 23 on rabies virus multiplication were observed at non cytotoxic doses. Therefore HPA 23 contrasts with other antiviral drugs which do not inhibit rabies virus multiplication without affecting the viability of cells.

Antimony↗
PubMed1977

[Cytotoxic and antitumor activity of a new series of heterocyclic compounds: dipyrido (4,3-b) (3,4-f) indoles].

Among newly synthesized compounds derived from the dipyrido [4,3-b] [3,4-f] indole nucleus, two have proved to be particularly active in vitro and in vivo. Their cytotoxic effects on cultured cells have been determined. At non toxic doses, they displayed a pronounced inhibitory effect on experimental L1210 Leukemia. These compounds have a strong affinity for DNA molecules.

Animals↗
PubMed1976

Effect of ammonium 5-tungsto-2-antimoniate on encephalomyocarditis and vesicular stomatitis virus infections in mice.

Ammonium 5-tungsto-2-antimoniate (HPA 23) protected micr partially or completely against two strains of encephalomyocarditis (EMC) virus and one strain of vesicular stomatitis (VSV) virus. The best protective effect was obtained with EMC strain VR 129 and VSV when a single i.p. injection of HPA 23 was administered shortly before virus inoculation. Mice protected by HPA 23 against EMC strain VR129 had virus titres in the blood and brain similar to those in untreated mice. A synergism between interferon and HPA 23 was observed in mice infected with EMC VR129. Our results demonstrate the in vivo activity of HPA 23 against two lethal viral infections and suggest that, at least in mice infected with EMC, death may not be related solely to virus multiplication.

Animals↗