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Biomedical subjects

P Rathelot

Publications and source records attributed to P Rathelot.

13 recordsLinked to original sources

[Electron transfer reactions: from electrons to drugs].

Electron transfer reactions have been at the heart of great advances in organic and inorganic chemistry and biology since the early work in 1954 by H. Taube (Nobel Chemistry Prize in 1983) and R. Marcus (Nobel Chemistry Prize in 1991). In organic chemistry, a new kind of chain substitution reaction with paramagnetic species was defined and identified as S(RN)1 (substitution, radial-nucleophilic, unimolecular). In our laboratory, choosing more or less complex molecules which possess electron-withdrawing groups and correctly disposed alkylation sites has enabled us to extend this concept to the heterocyclic (S(RN)1 HET) and quinonic (S(RN)1 QUI) series. These studies led us to prepare, under mild operating conditions, highly branched molecules hard to obtain via other pathways and which possess high pharmacological activity in various fields. We have discovered new reaction mechanisms such as LD-S(RN)1 (long-distance S(RN)1) E(RC)1 (elimination radical chain, unimolecular), bis-S(RN)1 and poly-S(RN)1. Moreover, we have developed a new technology using microwaves which increases the interest of electron transfer reactions in medicinal chemistry for drugs synthesis.

Alkylation↗

Implication of nitro group reduction in the mutagenic and chromosome damaging activities of 22 new 5-nitroisoquinolines by the Salmonella mutagenicity test and the cytokinesis-blocked micronucleus assay.

The mutagenic (MUT) and chromosome-damaging (CHR) activities of 22 potential antimalarial drugs (5-nitroisoquinoline derivatives) were evaluated by the Salmonella test and the cytokinesis-blocked micronucleus assay (CBMN). The Salmonella mutagenicity test was performed with and without metabolic activation (S9 mix) in S. typhimurium strains TA100 and YG1042 (an overproducing nitroreductase and O-acetyltransferase TA100 strain). The CBMN was carried out on human lymphocytes without metabolic activation. Four concentrations were tested: 1, 10, 100 and 1000 ng/ml. MUT was expressed as minimal mutagenic concentrations (MMC, microM) and CHR was expressed as minimal chromosome-damaging concentrations (MCDC, nM) to compare both activities. All the 5-nitroisoquinoline compounds were mutagenic in TA100. MMC ranged from 0.1 to 52.9 microM in TA100. A statistically significant decrease in MMC was observed in YG1042 (8 x 10(-3) to 3.5 microM), implicating reduction of the nitro group. Modulation of MUT by S9 mix was not significant in TA100 and YG1042. CHR was detected in 13 products for at least one concentration. Among the chromosome-damaging compounds, the MCDC ranged from 2.9 x 10(-3) to 3.6 nM. No relationship was found between MUT and CHR, suggesting two distinct pathways of DNA damage.

Adolescent↗

Two new pyridine monoterpene alkaloids by chemical conversion of a commercial extract of harpagophytum procumbens

The treatment of harpagide (1), harpagoside (2), or 8-O-p-coumaroylharpagide (3), the main iridoids of Harpagophytum procumbens and Harpagophytum zeyheri, with NH3 and HCl led to aucubinine B(4), a pyridine monoterpene alkaloid (PMTA). A similar procedure applied to a commercial extract of H. procumbens yielded 4 and two new PMTAs named beatrine A (5) and beatrine B (6). The structures of these new PMTAs were established using ESIMS and 2D NMR. Their semisynthesis was analyzed in terms of reaction mechanisms.

Journal Article↗

[Semi-concentrated radiation of cerebral metastases of bronchial cancer].

Results of radiotherapy in 49 patients with cerebral metastases are reported, overall treatment including anti-edema therapy based on Synacthene and radiotherapy of the whole brain by delivering 17.5 grays in 5 days. Tolerance to treatment was good. Total, durable (more than 2 months) neurological remission was obtained in 50 p. cent of cases, duration of remission being a mean of 120 days in patients responding to therapy. Concentrated irradiation is therefore effective and useful in the treatment of cerebral metastases from bronchial cancer as it improves survival conditions.

Brain Neoplasms↗

[Radiotherapy of localized inoperable bronchial squamous cell carcinoma (author's transl)].

Authors have shown that in some favorable cases radiotherapy of localized bronchial carcinoma could give very good results. The study on the cases from 1960 to 1969 shows that authors have 8% of three years survival upon 105 patients who have been treated by 50 Grays or more in 5 weeks. The survival was better for the small cancers T2 than for the large ones. The study on the cases from 1970 to 1977 shows that to obtain 101 cases of squamous cell carcinoma (T2,4 -N0,2 -M0) authors were obliged to study 564 cases. The three years survival was 3,1% for carcinoma receiving more than 40 Grays/4 weeks. The survival is better for small cancer and for the cases without radiological mediastinal nodes. In conclusion, radiotherapy is the best treatment after surgery, limited disease can be cure, and iterative radiotherapy increases our results.

Bronchial Neoplasms↗