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 decahydrocyclopropa2′,3′]cyclohepta 1′,2′:3,4]benzo1,2-d]1,2,3]triazol-7(6H)-one was synthesized by a dipolar cycloaddition 1,3 between benzyl azide and α,β-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 ¹H and ¹³C 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 μM). In addition to using flow cytometry and the apoptosis assay, cell cycle arrest at the S phase (10 μM) and G2/M arrest in (5 and 10 μM) 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 μM 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.