Synthesis of Aminocholesterol Derivatives with Antibiotic Properties.-Cholesterol derivatives bearing an amino-or aminoalkyl substituent in position C-7 such as (IV), (VIII), and (X) have shown interesting biological activities. -(ELKIHEL, L.; BOURASS, J.; DHERBOMEZ, M.; LETOURNEUX, Y.; Synth.

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Synthesis and Evaluation of the Anti-Inflammatory Effects of Niflumic Acid Lipophilic Prodrugs in Brain Edema. -Five new lipophilic prodrugs of the non-steroidal anti-inflammatory drug niflumic acid (I) are presented and evaluated on the experimental brain edema by determination of the prostaglandin E2 brain-tissue concentration. Highest activities are observed with prodrugs (II) and ( III) and with niflumic acid itself, all of them being superior to dexamethasone. -(EL KIHEL, L.; BOURASS, J.; RICHOMME, P.; PETIT, J. Y.; LETOURNEUX, Y.; Arzneim.

Summary :DFMO, a trypanostatic drug, presents a satisfactory intestinal absorption but its elimination from the blood is rapid so that high doses are necessary to obtain a therapeutic effect. In this study, we propose a strategy to enhance the bioavailability of DFMO by using lipidomimetic derivatives. Three lipidomimetic DFMO derivatives called ODFMO, S-DFMO and Chol-DFMO were designed to reach easily the plasma and to be cleaved preferentially by plasma esterases progressively liberating free DFMO. Chol-DFMO only could be cleaved partially whereas the other compounds appeared to be stable in a reconstituted intestinal medium and mouse plasma. Nevertheless, the use of DFMO derivatives in T. b. brucei experimental chemotherapy appeared as an interesting approach. Thus, ODFMO was trypanocidal in vitro whereas DFMO, the active principle, was only trypanostatic. Nevertheless, this compound did not release DFMO in mouse blood as expected and acted therefore not as a prodrug. Oral treatment using low doses of compound O-DFMO was able to cure 40 % mice while the active principle (eflornithine) administered at 50 fold higher molarity failed to cure any mice. This indicates that compound ODFMO acts by a specific mechanism which remains to be investigated. S-DFMO was less active and Chol-DFMO had no in vitro activity but released small amounts of DFMO in mice, however, too slight to obtain a therapeutic effect. KEY WORDS

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