4.4 Review

Chemical structure of phenothiazines and their biological activity

Journal

PHARMACOLOGICAL REPORTS
Volume 64, Issue 1, Pages 16-23

Publisher

POLISH ACAD SCIENCES INST PHARMACOLOGY
DOI: 10.1016/S1734-1140(12)70726-0

Keywords

phenothiazine derivatives; antipsychotics; calmodulin; protein kinase C; P-glycoprotein; multidrug resistance

Funding

  1. Polish Ministry of Sciences and Higher Education [N N204150338]
  2. Wroclaw Medical University [ST-413]

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Phenothiazines belong to the oldest, synthetic antipsychotic drugs, which do not have their precursor in the world of natural compounds. Apart from their fundamental neuroleptic action connected with the dopaminergic receptors blockade, phenothiazine derivatives also exert diverse biological activities, which account for their cancer chemopreventive-effect, as: calmodulin- and protein kinase C inhibitory-actions, anti-proliferative effect, inhibition of P-glycoprotein transport function and reversion of multidrug resistance. According to literature data on relations between chemical structure of phenothiazines and their biological effects, the main directions for further chemical modifications have been established. They are provided and discussed in this review paper.

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