Sappanin-type homoisoflavonoids from Scilla bisotunensis Speta.: Cytotoxicity, molecular docking, and chemotaxonomic significance

• Published in: Journal of molecular structure 2023-02, Vol.1273, p.134326, Article 134326
• Main Authors: Hafez Ghoran, Salar, Firuzi, Omidreza, Pirhadi, Somayeh, Khattab, Omar M., El-Seedi, Hesham R., Jassbi, Amir Reza
• Format: Article
• Language: English
• Subjects: Homoisoflavonoids; HT-29 cells; Liliaceae; Scilla bisotunensis speta; Scilla bisotunensiss peta; Src kinase domain inhibitors
• ISSN: 0022-2860; 1872-8014; 1872-8014
• DOI: 10.1016/j.molstruc.2022.134326

•Isolation and characterization of nine sappinane-4-one type homoisoflavonoids from the bulbs of Scilla bisotunensis Speta.•In vitro cytotoxic effects of the homoisoflavonoids against HT-29 colon cancer cells.•Determination of absolute configuration of sappinane-4-one homoisoflavonoids by circular dichroism experiment.•A salient binding affinity of bioactive homoisoflavonoids, 8 and 9, with the Src kinase domain enzyme.•Homoisoflavonoids 1‒3 and 5 are suggested as chemotaxonomic markers for S. bisotunensis. Phytochemical investigation of the chloroform extract of Scilla bisotunensis Speta. bulbs led to the isolation and structure elucidation of six sappinane-4-one (1-4, 7, 9) and three 3,9-dehydrosappinan-4-one (5, 6, 8) homoisoflavonoids. The structures of compounds 1-9 were established based on extensive NMR, ESIMS, UV, and ECD spectra, and also by comparison with the previously reported spectroscopic data. The in vitro cytotoxicity of sappanin-type homoisoflavonoids 1-9 was assayed against HT-29 human colorectal cancer cells using sulforhodamine B assay. Compounds 8 and 9 showed higher cytotoxic effects with IC50 of 5.3 and 6.1 µg/mL, respectively, while compounds 3, 5, and 7 exhibited moderate activity with IC50 ranging from 25 to 37 µg/mL. Interestingly, molecular docking studies revealed that compounds 1‒9 could be potential sarcoma kinase domain inhibitors with binding energies ranging from ‒7.37 (6) to ‒8.34 (9) kcal/mol when compared with the native inhibitor, purvalanol A of ‒7.90 kcal/mol. All homoisoflavonoids, except 1 and 5 are reported for the first time in a member of the Scilla genus, while, to the best of our knowledge this is the first phytochemical and biological study on S. bisotunensis. The plant exhibited good chemotaxonomic relationships to the genus Eucomis L'Hér. on the basis of comparing their chemical constituents with those reported in the related plant families. [Display omitted]