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

Turanll, Sümeyye
Nalbat, Esra
Güntekin Ergün, Sezen
Akhan Güzelcan, Ece
Muyan, Mesut
Cetin-Atalay, Rengul
Çallşkan, Burcu
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.


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Chiral pyridines as organocatalysts have been used in asymmetric organic synthesis in recent years. The asymmetric synthesis of camphor fused pyridine type novel organocatalysts were perfomed starting from cheap and easily available natural (+)-camphor. Using camphor fused pyridine skeleton, six organocatalysts 29, 32, 33, 38, 40, and 41were successfully synthesized. The first four nucleophilic and Lewis base catalysts 29, 32, and 33 are different P-oxides and P,N-dioxides which were tested in allylation of...
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Citation Formats
S. Turanll et al., “Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with in Vitro Growth Inhibitory and in Vivo Antitumor Activity,” ACS Omega, vol. 7, no. 41, pp. 36206–36226, 2022, Accessed: 00, 2023. [Online]. Available: