2-Amino diphenylsulfides as new inhibitors of trypanothione reductase.

Trypanothione reductase (TR) is the primary enzyme responsible for the reduction of trypanothione, the analog of glutathione found in trypanosomatidae. We have discovered a series of diphenylsulfides which are potent inhibitors of TR and have no activity on mammalian glutathione reductase. These compounds are also active in vitro on various stages of the parasite. Although structurally related to phenothiazines, which are known to be TR inhibitors, these compounds are devoided of any neuroleptic activity, making them attractive leads to develop specific and non toxic anti-chagasic drugs.

Synthesis of epoxypropyloxy chromones and allyl hydroxy chromones and in vitro-in vivo activity on protoscoleces of Echinococcus multilocularis (Cestoda).

Derivatives with epoxypropyloxy, allyloxy and allyl hydroxychromone structures were synthesized and tested against protoscoleces of Echinococcus multilocularis. Compounds IV-IX were tested in vitro and compound VII proved the most active of them with, at 0.1 mmol.L-1, 98% dead protoscoleces in open vesicles after 24 hours and 80% in closed vesicles within 96 hours. Compound VII was tested in vivo on Meriones unguiculatus infested by Echinococcus multilocularis, but was found to be rather inactive.

Substituted phenylthiophenylamines with antiinflammatory activity.

Several acid and closely related non acid derivatives of 2-phenylthio- and 4-phenylthio-N-acyl phenylamines have been synthesized and tested in vivo, on the carrageenan RFE assay, and in vitro, on prostaglandin synthesis inhibition assay. Compound (XV c), bearing a propanoic acid substituent together with a p-chlorobenzoyl group situated on nitrogen atom in the 2-position, showed a 79% edema reduction (300 mg/kg p.o.) 6 hours after carrageenan injection, but no activity in vitro. The benzyl alcohols (XIV m) and (XIV n), on the contrary, inhibited PG synthesis; their lack of activity in vivo could be interpreted as the result of their oxidation to the inactive benzoic acids (XIV g) and (XIV h).

[7-Chloro(phenylthio)-4-phenylaminoquinolines. Study of its anti-inflammatory and analgesic activity]. / Chloro-7 (phénylthio)phénylamino-4 quinoléines. Etude de l'activité antiinflammatoire et analgésique.

Some 7-chloro(phenylthio)-4-phenylaminoquinolines substituted in the benzene rings were prepared and subject to the Winter test for potential antiinflammatory activity and the acetic acid test for analgesic activity. Derivative (I) was devoid of antiinflammatory properties but showed interesting analgesic activity although this was 30 times weaker than that of indomethacin used as reference substance. The DL50/DE50 ratio is greater than 16 for derivative (I) and 3 for indomethacin. The other compounds had no or only slight activity.

[Inhibition of prostaglandin synthesis by (phenylthio-4 phenylamino)-2 nicotinic acids]. / Inhibition de la synthèse des prostaglandines par des acides (phénylthio-4 phénylamino)-2 nicotiniques.

In the rat, (phenylthio-4 phenylamino)-2 nicotinic and [(chloro-4 phenylthio)-4 phenylamino]-2 nicotinic acids inhibit the hypotensive prostaglandin-mediated action of arachidonic acid. They inhibit also the formation from arachidonic acid, of prostaglandin-like substances by chopped rat lungs and of malonaldehyde by rat platelets. They are prostaglandin synthetase inhibitors, three to ten times less active as indomethacin.