New enaminone sesquiterpenic: TiCl4-catalyzed synthesis, spectral characterization, crystal structure, Hirshfeld surface analysis, DFT studies and cytotoxic activity

In this work, the compound 2 named ethyl (1,1-dichloro-1a,5,5,7-tetramethyl-8-oxo-1a,2,3,4,5,5a,8,9-octahydro-1H-benzo[a]cyclopropa[b][7]annulen-6-yl)glycinate (C20H29Cl2NO3) was synthesized from the alpha,beta-unsaturated sesquiterpene ketone 1 using the azido-Schmidt reaction catalyzed by titanium tetrachloride (TiCl4). The structure of the newly synthesized enaminone 2 was fully identified using its HRMS, FT-IR, UV-Visible, NMR (H-1 & C-13), and X-ray crystallography analyses. The compounds 1 and 2 were tested for their cytotoxic activity in four human cancer cell lines, fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast (MCF-7 and MDA-MB-231). The obtained results showe that compound 1 is the most active against HT-1080 and A-549 cells with IC50 values from 13.28 to 16.41 mu M. The results of theoretical studies used to predict the molecular proprieties that lead to a high potential of cytotoxic effect are in perfect agreement with the experimental results. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, compound 2 was successfully synthesized using the azido-Schmidt reaction, and its structure was fully identified through various analyses. Compounds 1 and 2 demonstrated cytotoxic activity in human cancer cells, with compound 1 showing the highest activity against HT-1080 and A-549 cells. The theoretical studies on molecular properties were in agreement with the experimental results.