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.

Graphical Abstract

Keywords:

• Cancer
• cloves
• cytotoxicity
• essential oil
• eugenol
• 123-triazole
• isoxazoline