Journal
CHEMISTRY & BIODIVERSITY
Volume 19, Issue 7, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbdv.202100836
Keywords
thiazolidinone; crystal structure; cancer; apoptosis; molecular docking
Funding
- University Cadi Ayyad
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A series of novel compounds were synthesized from limonaketone and evaluated for their cytotoxic activity against human cancer cell lines. Thiazolidinones 9 and 10 showed strong anticancer activity in HT-1080 cell lines, with compound 10 exhibiting the highest ability to induce apoptosis and activate caspase-3/7. Molecular docking analysis indicated that compounds 9 and 10 formed stable ligand-caspase-3 complexes, with the presence of a phenyl group in compound 10 enhancing caspase-3 activation through additional hydrogen bonds with specific amino acids.
A series of novel 2-iminothiazolidin-4-one analogs have been synthesized from limonaketone, and structurally characterized by HR-MS, H-1-NMR and C-13-NMR spectroscopy techniques, and the structure of compound 4 was elucidated by XRD. The newly synthesized products were biologically evaluated in vitro for their cytotoxic activity against human cancer cell lines HT-1080, A549, and MCF-7. Thiazolidinones 9 and 10 were the most active compounds in HT-1080 cell lines (IC50=15.85 +/- 1.75 and 16.13 +/- 1.55 mu M, respectively). The apoptosis induction of the derivatives 9 and 10 were studied using annexin V staining, caspase-3/7 activity and cell cycle analysis. Compound 10 showed the highest ability of apoptosis induction and caspase-3/7 activation associated with S-phase growth arrest in HT-1080. Meanwhile, compound 9 has a moderate apoptotic effect and G0/G1-phase arrest in the after-mentioned cell. The molecular docking suggested that compounds 9 and 10 formed stable ligand-caspase-3 complexes. Besides, the presence of phenyl moiety in ligand 10 is responsible for the enhancement of the caspase-3 activation by the apparition of two additional hydrogen bonds with Cys163 and Gln161amino acids.
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