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-?hloro-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).