Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on leishmania major growth and trypanosoma brucei trypanothione reductase
A number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against Leishmania major (L. major) promastigotes. Several analogs were remarkably potent inhibitors, with antileishmanial activities being co...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 January 2016
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| In: |
European journal of medicinal chemistry
Year: 2015, Volume: 108, Pages: 436-443 |
| ISSN: | 1768-3254 |
| DOI: | 10.1016/j.ejmech.2015.11.023 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: http://dx.doi.org/10.1016/j.ejmech.2015.11.023
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| Author Notes: | Ana Marcu, Uta Schurigt, Klaus Müller, Heidrun Moll, R. Luise Krauth-Siegel, Helge Prinz |
| Summary: | A number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against Leishmania major (L. major) promastigotes. Several analogs were remarkably potent inhibitors, with antileishmanial activities being comparable or superior to those of the reference antiprotozoal drugs. Furthermore, we explored the structure-activity relationships of N-10 haloacetamides that influence the potency of such analogs toward inhibition of L. major promastigote growth in vitro. With respect to the mechanism of action, selected compounds were evaluated for time-dependent inactivation of Trypanosoma brucei trypanothione reductase. Our results are indicative of a covalent interaction which could account for potent antiprotozoal activities. |
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| Item Description: | Available online 23 November 2015 Gesehen am 07.05.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1768-3254 |
| DOI: | 10.1016/j.ejmech.2015.11.023 |