Synthesis and Anticancer Evaluation of Some Phenothiazine Derivatives

Abstract

10H-Phenothiazine 1 reacts with 2-chloroacetonitrile to give 2-(10H-phenothiazin-10-yl)- acetonitrile 2, which upon reaction with sodium azide gives the corresponding tetrazole 3. Treatment of 2 by either hydrazine hydrate or hydroxylamine affords 2-(2-chloro-10H-phenothiazin-10-yl)acetimidohydrazide 4 and 2-(2-сhloro-10H-phenothiazin-10-yl)-N'-hydroxyacetimidamide 7, respectively. Reaction of 4 with CS2 leads to the thione derivative 5. Treatment of 7 with acetic anhydride gives 3-[(2-chloro-10H-phenothiazin-10- yl)methyl]-4,5-dihydro-1,2,4-oxadiazole 8. Alkylation of sodium salt of compounds 3, 5, 6, or 8 by 1-chloro-2- methoxyethane and/or 2-(2-chloroethoxy)ethanol leads to the corresponding acyclic derivatives 9–16. Structures of all newly synthesized compounds are confirmed by IR, NMR and mass spectroscopy. All of the synthesized compounds demonstrate high activity against breast cancer cell line (MCF7).