Synthesis, Characterization, and Anticancer Evaluation of Some Heterocycles Bearing Chloroquinoline Moiety

Abstract— The reaction of 2-thiouracil or theophylline with phosphacumulene ylides furnished phosphoranylidene pyrimidinone or phosphanylidene purine diones, respectively. The formation of phenylaminoazetone and phenyliminoazetamine was observed when 2-chloroquinoline phenylhydrazine was reacted with phosphacumulenes. On the other hand, Lawesson’s reagent can be transformed by reaction with 2-thiouracil or theophylline into pyrimidine dithione and thioxopurinone, respectively. Treatment of 2-chloro-phenylhydrazonoquinoline with Lawesson’s or Japanese reagent under reflux conditions afforded 2-chloroquinoline derivatives, but the dimer was isolated when the same reaction was applied at room temperature. Further reaction of chloro(hydrazineylidenemethyl)quinoline with Lawesson’s or Japanese reagents under reflux provided the corresponding chloroquinoline derivatives. In addition, treatment of chloroquinoline oxime with Lawesson’s reagent at room temperature afforded chloroquinoline thiohydroxylamine, but phosphinodithioic acid and diazetidinedithiol-2-chloroquinoline were isolated when the same reaction was carried out under reflux. The effect of some of the tested compounds on membrane permeability in human colorectal carcinoma (HCT-116), human liver carcinoma (HepG-2) and human breast adenocarcinoma cells (MCF-7) were examined. Majority of the tested compounds have potent anticancer activity.