Synthesis and Anticancer Evaluation of Novel Derivatives of Isoxazolo[4,5- e][1,2,4]triazepine Derivatives and Potential Inhibitors of Protein Kinase C

Edwin Wagner; Joanna Wietrzyk; Mateusz Psurski; Lilianna Becan; Eliza Turlej

doi:10.1021/acsomega.0c03801

Synthesis and Anticancer Evaluation of Novel Derivatives of Isoxazolo[4,5- e][1,2,4]triazepine Derivatives and Potential Inhibitors of Protein Kinase C

ACS Omega. 2020 Dec 24;6(1):119-134. doi: 10.1021/acsomega.0c03801. eCollection 2021 Jan 12.

Authors

Edwin Wagner¹, Joanna Wietrzyk², Mateusz Psurski², Lilianna Becan¹, Eliza Turlej²

Affiliations

¹ Department of Drugs Technology, Wroclaw Medical University, Wroclaw 50-367, Poland.
² Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy Sciences, Wroclaw 53-114, Poland.

Abstract

In the present study, using Thorpe's reaction with Gewald's modification, 4-acetylamino-5-acetyl or 5-benzoyl 3-carboxamide compounds 3 or 4 were obtained. From these compounds, two series of compounds (5, 7, and 9 and 6, 8, and 10) were obtained with 98% hydrazine. Compounds 6, 7, 8, and 9 were then reacted with the appropriate aldehydes to afford a series of new isoxazole derivatives (11-18, 27-36, and 37-41) and the main compounds, 19-26 and 42-45, were isoxazolo[4,5-e][1,2,4]triazepine derivatives. The anticarcinogenic activities of selected compounds were tested on six lines of cancer cells, and their activities were compared with the relevant concentrations of the anticarcinogenic drugs cisplatin and doxorubicin in IITD PAN. Several compounds were tested on 60 lines of cancer cells by the NCI (Bethesda, MD, USA). The cyclization of compound 12 into derivative 46 was also carried out. Compound 21 showed extremely high antitumor activity.