Hybrid of the 1,2,3-triazole nucleus and sesquiterpene skeleton as a potential antitumor agent: Hemisynthesis, molecular structure, Hirshfeld surface analysis, density functional theory, and in vitro cytotoxic and apoptotic effects

A new 1,2,3-triazole sesquiterpenic named (4aR,5aS,7aR,10aR,10bR)-10-benzyl-5,5-dichloro-1,1,4a,7a-tetramethyl-1,2,3,4,4a,5,7a,10,10a,10b decahydrocyclopropa[2 ',3 ']cyclohepta [1 ',2 ':3,4]benzo[1,2-d][1,2,3]triazol-7(6H)-one was synthesized by a dipolar cycloaddition 1,3 between benzyl azide and alpha,beta-unsaturated sesquiterpene ketone catalyzed by titanium tetrachloride TiCl4. It was obtained with a good yield and characterized using single-crystal X-ray diffraction technique, infra red (IR) spectroscopy, High Resolution Mass Spectrometry (HRMS), UV-Visible, and H-1 and C-13 NMR spectroscopies. The optimization by the density functional theory (DFT) method was carried out to study the formation mechanism of the derivative. The selected compounds 1-4 exhibited anticancer activities in vitro against namely fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast (MCF-7 and MDA-MB-231 cell lines with IC50 in the range of 10.02-44.71 mu M). In addition to using flow cytometry and the apoptosis assay, cell cycle arrest at the S phase (10 mu M) and G2/M arrest in (5 and 10 mu M) was performed for compound 4 in fibrosarcoma (HT-1080) cancer cells. Results suggested that compound 4 test with good activity against HT-1080 cells with IC50 value from 10.02 mu M and induced the apoptotic effect. Theoretical studies were realized to estimate the molecular proprieties that lead to a high potential of cytotoxic effect, which is in agreement with the experimental results.