Synthesis and biological activities of some new phosphorus compounds containing pyranopyrazole moiety

Abstract

A simple method for construction of functionalized pyranopyrazoles containing phosphoramide and phosphonate groups via one-pot reaction was achieved. The methodology depended on the reaction of 6-amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (3) with triethyl phosphite and hexaethylphosphoramide and so with diethyl phosphite in the presence of chloroacetyl chloride or carbon disulfide. The products were screened for their antimicrobial, antioxidant and antiproliferative properties. Compound 7 displayed promising antimicrobial and antioxidative properties. Also, compound 8 showed potent cytotoxic effects against MCF-7, HepG-2 and HCT-116 cancer cells with IC50 values in range 5.3 ± 0.9 to 7.5 ± 0.6 μg/mL. Acridine orange and ethidium bromide were used for the detection of viable, apoptotic, and necrotic cells. The early apoptotic cell death was observed by the compounds in all types of the treated cells. Compounds 5, 7 and 8 induced high percentage of necrosis towards all treated cells. The late apoptosis was recorded as a high rate after treatment with compound 3 in HepG-2 cells.