Design, synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase, anti-xanthine oxidase, and cytotoxic activities.

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes2a–ehas been accomplished by reaction of 2-acetonitrile derivatives1a–ewith hydroxylamine. Cyclocondensation reaction of precursors2a–ewith some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives3a–e,4a–e, and5a–e, respectively. On the other hand, the reaction of precursors2a–ewith 2-chloropropanoyl chloride afforded the new acetimidamides6a–ewhich evolve under reflux of toluene to the new oxadiazoles7a–e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i)5awas the most active (IC50 = 4.0 μM) and selective against MCF-7 and (ii)2awas cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 μM, respectively) while2eis highly selective against OVCAR-3 (IC50 = 10 μM). [ABSTRACT FROM PUBLISHER]