Diseño, síntesis y evaluación biológica de un grupo de pirazinoisoquinolinas y quinolinas con posible actividad esquistosomicida y leishmanicida respectivamente
Schistosomiasis and leishmaniasis are two parasitic diseases well spread in the world, and at the same time both have very few medications for their treatment. For schistosomiasis, praziquantel (PZQ) is the drug of choice for its treatment, while in the case of leishmaniasis, the pentavalent antimon...
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2013
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| Online Access: | http://hdl.handle.net/10872/2785 |
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| Summary: | Schistosomiasis and leishmaniasis are two parasitic diseases well spread in the world, and at the same time both have very few medications for their treatment. For schistosomiasis, praziquantel (PZQ) is the drug of choice for its treatment, while in the case of leishmaniasis, the pentavalent antimonials used as first line drugs are highly toxic or present resistance problems. This work describes the design, synthesis and biological activity studies of a group of pirazinoisoquinolines and substituted quinolines with a possible schistosomicidal and leishmanicidal activities, respectively. After several intents, it was possible to synthesize PZQ and some related compounds (fifteen) through a sequence of five steps, with yields between 20 and 60%. PZQ was obtained with a yield of 33%, with a levo enantiomeric excess, and showed a better activity than the commercial compound. The related compounds obtained, evaluated against S. mansoni strains did not have an activity comparable to that of PZQ, at the concentrations evaluated. Quantitative structure–activity relationships (QSAR) studies were also performed with PZQ derivatives reported in the literature. Several ways of synthesis were also probed for the possible leishmanicidal compounds proposed, until it was possible to obtain twenty two quinoline derivatives (of the type 2-methyl-, 2-propyl-, 4-methyl-2-propyl- and 2-alquildiamino-), with yields between 10 and 70%. Of the compounds evaluated, two showed promising activity against L. mexicana promastigotes, 2-methylquinoline and 6,7-methylendioxi-2-propyl-quinoline. QSAR studies with these compounds did not yield a representative model for the set. |
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