Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity

Abstract

The vicinal diaryl heterocyclic framework has been widely used for the development of compounds with significant bioactivities. In this study, a series of diaryl heterocycles were designed and synthesized based on an in-house diaryl isoxazole derivative (9), and most of the newly synthesized derivatives demonstrated moderate to good antiproliferative activities against a panel of hepatocellular carcinoma and breast cancer cells, exemplified with the diaryl isoxazole 11 and the diaryl pyrazole 85 with IC50 values in the range of 0.7–9.5 μM. Treatments with both 11 and 85 induced apoptosis in these tumor cells, and they displayed antitumor activity in vivo in the Mahlavu hepatocellular carcinoma and the MDA-MB-231 breast cancer xenograft models, indicating that these compounds could be considered as leads for further development of antitumor agents. Important structural features of this compound class for the antitumor activity have also been proposed, which warrant further exploration to guide the design of new and more potent diaryl heterocycles.

Synthesis and Antimicrobial Activity of some Ester Functionalized Isoxazoles incorporating Anthracene Moieties via Nucleophilic Substitution Reaction

“…024 2 214 important component of heterocyclics. 12,13 A variety of synthetic protocols for producing the isoxazole core have been explored. 14 The condensation reaction of hydroxyl amine with each 1,3-dicarbonyl compound, α,β-unsaturated carbonyl compounds and nitriles are used in the classical approach for the synthesis of these remarkable compounds.…”