An expedient synthesis of novel spiro[indenoquinoxaline-pyrrolizidine]-pyrazole conjugates with anticancer activity from 1,5-diarylpent-4-ene-1,3-diones through the 1,3-dipolar cycloaddition/cyclocondensation sequence

Abstract

Endo-1,3-Dipolar cycloaddition of azomethine ylides generated in situ from 11H-indeno[1,2-b]quinoxalin-11-one and L-proline/thiaproline to (E)-1,5-diarylpent-4-ene-1,3-diones led to the 3-hydroxy-3-aryl-1-(1′-arylspiro[indeno[1,2-b]quinoxaline-11,3′-(thia)pyrrolizidin]-2′-yl)prop-2-en-1-ones containing the 1,3-diketone fragment. Upon processing of these adducts with arylhydrazine hydrochlorides in an acidic medium, the 2′-(1,3-diaryl-1H-pyrazol-5-yl)-1′-arylspiro[indeno[1,2-b]quinoxaline-11,3′-pyrrolizidines] were formed as individual regioisomers. In a similar reaction with hydrazine hydrate and hydroxylamine, the corresponding hybrids bearing the N-unsubstituted pyrazole and isoxazole moieties were obtained. Most of spiro[indenoquinoxaline-pyrrolizidine]-N-arylpyrazole conjugates have shown high cytotoxic activity against the HeLa cancer cell line.