Synthesis and pharmacological investigation of new N-hydroxyalkyl-2-aminophenothiazines exhibiting marked MDR inhibitory effect |
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| Authors: | Daniella Takács Orsolya Egyed László Drahos Pál Szabó Katalin Jemnitz Mónika Szabó Zsuzsa Veres Júlia Visy József Molnár Zsuzsanna Riedl György Hajós |
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| Institution: | 1. Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59, H-1025 Budapest, Hungary;2. Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59, H-1025 Budapest, Hungary;3. Department of Medical Microbiology, University of Szeged, Dóm tér 10, H-6720 Szeged, Hungary |
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| Abstract: | Novel N-hydroxyalkyl-2-aminophenothiazines implying a tetrazole moiety at the alkyl chain have been synthesized by hydroboration–oxidation of dienes followed by Buchwald–Hartwig cross-coupling reaction. Also, some sulfoxide and sulfone derivatives have been prepared by selective oxidations. MDR inhibition studies on rat hepatocyte cell culture revealed that some derivatives exhibit marked biological efficacy exceeding that of the standard verapamil (e.g., 3h, 4h, 16). Selected derivatives were subjected to chemical resolution to provide both enantiomers which were shown of similar activity on P-gp interaction measurements. The new compounds exhibited no toxicity. |
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| Keywords: | Sulfoxide and sulfone derivatives MDR inhibition Buchwald–Hartwig cross-coupling reaction Resolution of racemate |
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