Synthesis and biological evaluation of novel isoxazolines linked via piperazine to 2- benzoisothiazoles as potent apoptotic agents

Research paper by Sathish Byrappa, M. Harsha Raj, Tenzin Kungyal, Narayana U. Kudva N, Bharathi P. Salimath, K.M. Lokanatha Rai

Indexed on: 10 Oct '16Published on: 29 Sep '16Published in: European Journal of Medicinal Chemistry


Synthesis of 3-(4-((3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl)piperazin-1-yl) benzoisothiazole derivatives (5a-i), which constitute a new class of isoxazolines, has been accomplished in regio-selective manner. These derivatives have been prepared by employing the reaction between substituted aldoximes (4a-i) and 3-(4-Allylpiperazin-1-yl) benzoisothiazole in presence of chloramine-T which afforded in good yields. These compounds were screened for cytotoxic activity on tumor cells. Four among the nine synthesized compounds were found to exhibit potent cytotoxic and antineoplastic activities in comparison to tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in mammalian cancer cells. The rest of the derivatives showed moderate activity.

Graphical abstract 10.1016/j.ejmech.2016.09.094.jpg
Figure 10.1016/j.ejmech.2016.09.094.0.jpg
Figure 10.1016/j.ejmech.2016.09.094.1.jpg
Figure 10.1016/j.ejmech.2016.09.094.2.jpg
Figure 10.1016/j.ejmech.2016.09.094.3.jpg
Figure 10.1016/j.ejmech.2016.09.094.4.jpg