Abstract EN:

The studies presented in this thesis focused on the in vitro effectiveness of twelve 2-benzamido-5-nitro thiazole (BNT) derivatives substituted on the benzene ring on three species: Lymnaea peregra ovata, Gammarus pulex pulex and Euglena gracilis. The results obtained were compared with those provided by a reference product, niclosamide. The intoxication of L. P. Ovata and G. P. Pulex by the derivatives of BNT or niclosamide was studied at first. Most L. P. Ovata showed an emersion during the first contact with one or the other of the toxic products and this process was even faster when the product was concentrated. Subsequent retraction of the animal into its shell usually preceded its death. The reproductive activity of the snail was disturbed with a decrease in the number of egg-masses. The amplitude of G. P. Pulex displacements only decreased at high concentrations of toxic; the movements of its pleopods were then increased. The determination of the LC50 was performed with the 13 products in both species. The value of this parameter gradually decreased in inverse proportion to the exposure time and tended towards a zero limit. The most effective products had a halogenated substituent in the meta position and were generally bisubstituted. The increase in toxicity over time was lower in G. P. Pulex than in L. P. Ovata. The toxicity of BNT was close to that of niclosamide. The second part of this work focused on the intoxication of E. Gracilis by BNT derivatives or niclosamide. The products acted by inducing a delay in cell growth, a decrease in the maximum number of algae per millilitre and causing their death. The cultivation of algae at pH 3. 5 and at pH 7. 2 was used to study the effectiveness of the protonated and neutral forms of the molecules. The products showed a difference of activity according to the pH: their toxicity could be higher in an acid medium than in a neutral medium. The effectiveness of BNT derivatives was estimated using three parameters: LC50, IC50 and ACmax. If the LC50s and IC50s are considered in relation to exposure time, we have noted a fall to a minimum with a subsequent maintenance at this minimum or an increase. The most effective products were usually those that had a substituent in the meta position. In addition, these derivatives were generally bisubstituted. The toxicity of niclosamide was generally lower than that of the most effective BNT derivatives. ACmax values were close to the LC50 values of L. P. Ovata or G. P. Pulex. The results obtained with the three species enabled to study the relationships between the activity of the products and their structure. The toxicity parameters (LC50 or IC50) were expressed in relation to the physicochemical parameters of the molecules (octanol/water partition coefficient, alkaline hydrolysis rate constant) or the parameters of the substituents (π of Hasch, σ of Hammett). The results showed that the toxicity increased with lipophilicity and generally decreased with the electro-attractive effect of the substituents, except for E. Gracilis at acid pH where the attractive effect increased the toxicity. The pKa did not intervene in these relations, whatever the species studied.