N-acetyl-beta-D-hexosaminidase from Trichomonas vaginalis: substrate specificity and activity of inhibitors.

Among chitinolytic activities previously described in Trichomonas vaginalis, N-acetyl-beta-D-hexosaminidase (NAHase) was the enzyme system expressing the highest level of specific activity. We report here some biochemical characteristics of NAHase purified from T. vaginalis. We found at first that the use of 4-methylumbellifferyl-substrate was responsible for a substrate affinity for the enzyme, about 1000-fold higher than those when using p-nitrophenyl-substrates (PNP). Whereas the optimum pH was 7.0 using PNP-substrate, it was at 4.5 using 4-methylumbelliferyl-substrate. Four different substrates were compared for their action on T. vaginalis NAHase and we have found that N-acetyl-beta-D-glucosaminide substrate was the most specific. DTT had no effect on enzyme activity suggesting that thiol group are not involved at the catalytic site. The use of previously described inhibitors showed a positive correlation between trichomonacidal activity and NAHase inhibition.

Synthesis and biological evaluation of ureido and thioureido derivatives of 2-amino-2-deoxy-D-glucose and related aminoalcohols as N-acetyl-beta-D-hexosaminidase inhibitors.

Ureido and thioureido derivatives of 2-acetamido-2-deoxy-beta-D-glucose, 1-amino-1-deoxy-D-glucitol and 2-(2-aminoethoxy)ethanol were prepared as N-acetyl-beta-D-hexosaminidase (NAHase) inhibitors and were evaluated on Trichomonas vaginalis NAHase. Although none showed complete inhibition of the enzyme at 100 microM, 1-amino-1-deoxy-D-glucitol derivatives acted as competitive inhibitors of the NAHase of T. vaginalis.

Synthesis and nematocidal activity of arylmercaptovinyltetrahydropyrimidines.

A set of mercaptovinyl tetrahydropyrimidines was synthesized in good yields by lithiation of 1,2-dimethyltetrahydropyrimidine with n-butyl lithium in tetrahydrofurane, followed by condensation with aromatic thioesters. Against three nematode genera, anthelminthic screening shows little activity; 2b and 2d were the most potent against Molinema dessetae.

Synthesis and anthelminthic evaluation of 2-amidino-1,3,4-oxa and 1,3,4-thiadiazoles, structurally related to tetramisole.

N-(1,3,4-thiadiazol-2-yl) 1a-1k and N-(1,3,4-oxadiazol-2-yl-) amidines 2a-2g, N-(1,3-thiazol-2-yl) 3a, 3b and N-(1,3-benzothiazol-2-yl-)amidines 4a, 4b were synthesized and tested as anthelminthics, in vitro, against a free nematode (Rhabditis pseudoelongata), against infecting larvae of an intestinal parasite of rats (Nippostrongylus brasiliensis) and against infecting larvae of a filaria (Molinema dessetae).

[Synthesis of 2-aryl benzothiazoles and research on its antiparasitic activity]. / Synthèse d'aryl-2 benzothiazoles et recherche d'activité antiparasitaire.

Several 2-aryl benzothiazoles (with phenyl, naphthyl, thienyl and some oxygenated heterocycles) were synthesized. The anti-parasitic properties of these compounds were evaluated, in vitro and in vivo, against one Nematode Nippostrongylus brasiliensis and, in vitro against two Protozoaires Entamoeba histolytica and Trichomonas vaginalis. Only two compounds exhibited, in vitro a low nematicidal activity.

[Dihydro-5,6-imidazo[2,1-b]thiazoles, dihydro-2,3-imidazo[2,1-b]benzothiazoles, analogs of levamisole]. / Dihydro-5,6 imidazo[2,1-b]thiazoles, dihydro-2,3 imidazo[2,1-b]benzothiazoles, analogues du levamisole.

New compounds containing 5,6-dihydro imidazo[2,1-b]thiazole, 2,3,5,6-tetrahydro imidazo[2,1-b]thiazole and 2,3-dihydro imidazo[2,1-b]benzothiazole rings, substituted by heterocycles analogue to chromones, were synthesized and screened against three nematodes, in vitro. The results indicate moderate anthelmintic properties, compared to levamisole; nevertheless, some products exhibit a significant degree of activity.

[On the plurifactorial determinism of the organophosphorous-induced teratogenesis on bird embryos; trials of protection by various compounds: oximes, hydroxamic acids and nicotinamide analogs (author's transl)]. / Sur le determinisme plurifactoriel de la tératogénèse induite par les dérivés organophosphores chez l'oiseau; essais de protection des troubles morphogénétiques par divers composés: oximes, acides hydroxamiques et analogues de la nicotinamide.

Simple methods were applied to study the teratogenesis in Quail embryos induced by two important organophosphorous compounds: parathion and dicrotophos. Parathion led only to vertebral malformations, as other natural and synthetic cholinomimetics: nicotine, carbamylcholine, decamethonium, neostigmine... Dicrotophos induced not only vertebral malformations (specific to neuromuscular junction poisons) but also beak, legs and feather abnormalities (peripheric malformations which are also produced by insuline and sulfanilamide). Oximes and hydroxamic acids, some of these being analogs of nicotinamide, were tested as antiteratogens. The 3-(CO-NH2), or -(CO-NHOH), substituted pyridinic compounds (nicotinamide, nicotinohydroxamic acid) prevent perfectly dicrotophos-induced beak and legs malformations, in tertiary amine form, but very little in quaternary amine form (methyliodide). The 4-substituted pyridinic compound (isonicotinohydroxamic acid) and aliphatic oxo-oximes were quite ineffecient against these malformations. The vertebral malformations, as a rule, were not lessened by the compounds tested, except for isonicotinoyl-formaldoxime methyl iodide and in some degree for nicotinohydroxamic acid. From these observations, it results that teratogenesis induced by compounds as dicrotophos is rule by a plurificatorial determinism. The beak and legs malformations are prevented by analogs of nicotinamide. In the contrary, the vertebral malformations induced by parathion or dicrotophos are nicotinamide unsensitive and are only prevented by powerful cholinesterase reactivators as pralidoxime or TMB4 (MEINIEL, 1976 b) but are reduced little or not at all by less potent cholinesterase reactivators (HEATH).