Synthesis and in vitro antitumor activity of novel ring D analogues of the marine pyridoacridine ascididemin: structure-activity relationship.

Marine compounds with pyridoacridine skeletons are known to exhibit interesting antitumor activities. Ascididemin has already been reported as displaying significant antitumor activities in vitro and has also been found to have a relatively high global toxicity in vivo. We synthesized a series of 16 analogues (among which 11 compounds were different from previously described ones) with the aim of developing new anticancer agents with significantly improved efficacy/tolerability ratios.

Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: comparison between mono- and bisquaternary ammonium salts.

On the basis of a previous structure-activity relationship study, we identified some essential parameters, e.g. electronegativity and lipophilicity, required for polar head analogues to inhibit Plasmodium falciparum phospholipid metabolism, leading to parasite death.

The design of original antimalarial drugs. An example of phospholipid metabolism.

The aim of our program was to find an original chemotherapeutical treatment (and eventually a preventive treatment) of malaria, an illness largely predominant in developing countries, by interfering on an essential metabolism developed by Plasmodium during its erythrocytic phase. Apart from what has been learnt about metabolism and the pharmacological target, a crucial step has been taken during this contract by passing from micromolar in vitro active concentrations (during 1986-1990) to nanomolar ones (during 1990). These compounds should naturally short-circuit resistance phenomena already established against drugs in current use, as has already been verified on polypharmacoresistant strains or isolates of P.

Mortality study among workers producing ferroalloys and stainless steel in France.

A mortality study was carried out among the workers of a plant that had produced ferrochromium and stainless steel, and was still producing stainless steel, in order to determine whether exposure to chromium compounds, to nickel compounds, and to polycyclic aromatic hydrocarbons (PAH) could result in a risk of lung cancer for the exposed workers. The cohort comprised 2269 men whose vital status were recorded between 1 January 1952 and 31 December 1982. The smoking habits of 67% of the cohort members were known from medical records.