Synthesis, characterization, and biological evaluation of new heterocyclic systems 1, 2, 3-triazole-isoxazoline from eugenol by the mixed condensation reactions

Abstract

We report the synthesis of new series of heterocyclic systems eugenol 1 derivatives by the mixed condensation reaction of 1,3-dipolar azide and the oxide of p-chlorophenylnitrile on the 4-allyl-2-methoxy-1-(prop-2-yn-1-yloxy)benzene 2. The mono and bicycloadducts, whose structure is homologous to compounds having a broad spectrum of activity, were obtained in good yields. The monocondensation reaction of azides on 4-allyl-2-methoxy-1-(prop-2-yn-1-yloxy)benzene 2 is completely chemoselective, regioselective and stereospecific. The condensation of nitrile oxide on 1,2,3-triazole monocycloadducts prepared was chemoselective and regioselective. The structure of all cycloadducts were characterized and confirmed by the 1H, 13C, 2D nuclear magnetic resonance and mass spectrometry analysis. All the newly synthesized mono and bis-heterocyclic compounds have been selected for their antiproliferative activity against HT-1080 fibrosarcoma, A549 lung carcinoma, and MCF-7 and MDA-MB-231 breast carcinoma cell lines. Among the derivatives, only the compounds 4a, 4b, 5a, 5b, 5d, 5e and 5g showed significant cytotoxicity with IC50 values ranging from 15.31 to 18.81 µM against HT-1080 cells, and 17.32 to 25.94 µM against the other cell lines.