ABSTRACT
INTRODUCTION: Leishmaniasis is an emergent orphan disease because of its co-infection with HIV AIDS. We report herein the in vitro biological evalution of five news quinolines, 2- or 3- substituted by an enyne group against Leishmania donovani (MHOM/ET/L82/LV9). PATIENTS AND METHODS: The quinolines has been synthesized by using a cross-coupling reaction between a chloroenyne and an organometallic coumpound in a presence of iron a "green" catalyst. Biological evalution is realized by a colorimetric method with the use of 3-(4,5-dimethylthiazol-2,5-diphényl)-tétrazolium bromide. RESULTS: Determination of the inhibitory concentrations as well as the minimal inhibitory concentrations has shown that the substitution by an enyne group made it possible to have a more important antileishmanial activity. In addition, we have seen that the -2 or the -3 position of the enyne group had no influence in the antileishmanial activity. CONCLUSION: Thus, we have shown the real interest of these quinolines which could be favourably compared with pentamidine, which is currently the reference product, and to consider the use of these quinolines in the treament of the leishmaniasis.
Subject(s)
Leishmaniasis/drug therapy , Quinolines/chemical synthesis , Quinolines/pharmacology , Humans , Molecular Structure , Structure-Activity RelationshipABSTRACT
INTRODUCTION: Leishmaniasis is an emergent orphan disease because of its co-infection with HIV AIDS. We report herein the in vitro biological evalution of five news quinolines, 2- or 3-substituted by an enyne group against Leishmania donovani (MHOM/ET/L82/LV9). PATIENTS AND METHODS: The quinolines has been synthesized by using a cross-coupling reaction between a chloroenyne and an organometallic coumpound in a presence of iron a "green" catalyst. Biological evalution is realized by a colorimetric method with the use of 3-(4,5-diméthylthiazol-2,5-diphényl)-tetrazolium bromide. RESULTS: Determination of the inhibitory concentrations as well as the minimal inhibitory concentrations has shown that the substitution by an enyne group made it possible to have a more important antileishmanial activity. In addition, we have seen that the -2 or the -3 position of the e nyne group h ad no influence in the antileishmanial activity. CONCLUSION: Thus, we have shown the real interest of these quinolines which could be favourably compared with pentamidine, which is currently the reference p roduct, and to consider the use of these quinolines in the treament of the leishmaniasis.
Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania donovani/drug effects , Quinolines/pharmacology , Animals , Parasitic Sensitivity TestsABSTRACT
Some perketals were synthesized by the Dussault procedure using simple bromides and 2-methoxyprop-2-yl hydroperoxide. Treatment with acetic acid gave the corresponding hydroperoxides. Both perketals and hydroperoxides were tested in vitro as trichomonacidal agents. Most of them exhibited very good activities. The most powerful compound was 2-methoxyprop-2-yl hexadec-l-yl peroxide which exhibited an IC50 value of 0.51 microM being 10 times more effective than the reference compound Metronidazole.
Subject(s)
Antitrichomonal Agents/chemical synthesis , Antitrichomonal Agents/pharmacology , Peroxides/chemical synthesis , Peroxides/pharmacology , Animals , Bromides/chemistry , Dose-Response Relationship, Drug , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Metronidazole/pharmacology , Structure-Activity Relationship , Trichomonas vaginalis/drug effectsABSTRACT
Two series of three trioxanes and 18 disubstituted peroxides were synthesised and evaluated for their in vitro trichomonacidal activity against Trichomonas vaginalis. The most active compound, 2-methylprop-2-yl 2-methoxyeth-1-yl peroxide exhibited an IC(50) value of 1.0+/-0.2 microM whereas other dialkyl peroxides had various IC(50) values which could not be correlated to their molecule structure. The best compound was about five times more active than metronidazole. The amount of generated oxygen or free radicals cannot explain completely the activity suggesting another way of action for these compounds on T. vaginalis.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Peroxides/chemical synthesis , Trichomonas vaginalis/drug effects , Animals , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Free Radicals/chemistry , Inhibitory Concentration 50 , Oxidants/chemistryABSTRACT
The synthesis of 2-substituted-trifluoromethylquinolines from aniline, trifluoromethylanilines, 3-aminoquinoline and trifluoromethylquinaldines is reported. In vitro antileishmanial evaluation of 2-alkyl, 2-alkenyl and 2-epoxypropyl-trifluoromethylquinolines is presented.