- (±)-trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents: Synthesis, in vitro evaluation and SAR analysis
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Leishmaniasis, a neglected tropical disease caused by parasites of the genus Leishmania, causes a serious burden of disease around the world, represents a threat to the life of millions of people, and therefore is a major public health problem. More effective and non-toxic new treatments are required, especially for visceral leishmaniasis, the most severe form of the disease. On the backdrop that dihydrobenzofurans have previously shown antileishmanial activity, we present here the synthesis of a set of seventy trans-2-phenyl-2,3-dihydrobenzofurans and evaluation of their in vitro activity against Leishmania donovani as well as a discussion of structure-activity relationships. Compounds 8m-o and 8r displayed the highest potency (IC50 4.6). Nonetheless, structural optimization as further requirement was inferred from the high clearance of the most potent compound (8m) observed during determination in vitro of its metabolic stability. On the other hand, chiral separation of 8m and subsequent biological evaluation of its enantiomers demonstrated no effect of chirality on activity and cytotoxicity. Holistic analysis of in silico ADME-like properties and ligand efficiency metrics by a simple scoring function estimating druglikeness highlighted compounds 16c, 18 and 23 as promising candidates for further development. Overall, the potential of trans-2-phenyl-2,3-dihydrobenzofurans as leishmanicidal agents was confirmed.
- Bernal, Freddy A.,Gerhards, Marcel,Kaiser, Marcel,Wünsch, Bernhard,Schmidt, Thomas J.
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- POLAROGRAPHIC AND CYCLIC VOLTAMMETRIC BEHAVIOUR OF SOME AZO COMPOUNDS DERIVED FROM SULFONAMIDE IN DMF-AQUEOUS SOLUTIONS
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The polarographic and cyclic voltammetric behaviour of (2-hydroxyphenylazo)-4-benzenesulfonamide and some of its derivatives have been studied in Britton-Robinson buffer series containing 30 vol.percent of DMF.Over the entire pH range (2-12), the reduction pathway occurs through an irreversible 4-electron step corresponding to the reduction of N=N center to the amine stage.The voltammograms recorded in acidic and alkaline solution at different scan rates exhibit one or two cathodic peaks depending on the substituent and the pH of the medium.The electrode reaction mechanism was suggested, also the kinetic parameters were calculated.
- Mabrouk, El-Sayed M.,Killa, Hamada M.,Fattah, Abdel Fattah A. Abdel,Yasen, Shalaby A.
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p. 268 - 275
(2007/10/02)
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