- Evaluation of synthetic substituted 1,2-dioxanes as novel agents against human leishmaniasis
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The treatment of human leishmaniasis is currently based on few compounds that are highly toxic, expensive and have a high rate of treatment failure. A number of recent studies on new drugs focuses on natural or semi-synthetic compounds. Among them, the endoperoxide artemisinin, extracted from Artemisia annua, and some of its derivatives have shown leishmanicidal activity. In the present work, a series of structurally simple, fully synthetic 1,2-dioxanes were evaluated for in vitro antileishmanial activity against promastigotes of Leishmania donovani; the cytotoxicity for mammalian cells was also assessed. The six most promising compounds in terms of activity and selectivity were further investigated for their antileishmanial activity on the promastigote forms of L. tropica, L. major and L. infantum and against L. donovani amastigotes. The good performance in terms of potency and selectivity makes these six hits promising candidates for a preliminary lead optimization as antileishmanial agents.
- Ortalli,Varani,Rosso,Quintavalla,Lombardo,Trombini
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- Thromboxane Synthetase Inhibitors and Antihypertensive Agents. 2. N--1H-isoindole-1,3-(2H)-diones and N--1H-isoindole-1,3(2H)-diones as Unique Antihypertensive Agents
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A series of N--1H-isoindole-1,3(2H)-diones were prepared as part of a continuing investigation into the biological properties of compounds that were both thromboxane synthetase inhibitors and potential antihypertensive agents.The most active thromboxane synthetase inhibition was found for the title imidazole derivatives wherein a hexyl or octyl chain separated the heterocyclic ends of the molecule (5,6) or with substitution on the isoindole portion of the molecule (18, 19, 21, 22, 25, 26).Compounds with shorter alkyl chain separations had good ant ihypertensive effects (1-5, 8-10, 19-22, 27-30).Butyl derivative 3 was chosen for further evaluation as a potential antihypertensive agent with thromboxane synthetase inhibitory properties.
- Press, Jeffery B.,Wright, William B.,Chan, Peter S.,Marsico, Joseph W.,Haug, Margie F.,et al.
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p. 816 - 819
(2007/10/02)
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