关键词: 异海松酸, 酰氨基硫脲, 抗肿瘤活性, 分子对接

Using the natural product isopimaric acid as a starting material, nine N-isopimaroyl-N'-aryl acylamino thiourea derivatives were designed and synthesized through functional group assembly strategy. The MTT assay was used to evaluate the inhibitory activity of these compounds against four human cancer cells HepG-2, K562, MCF-7 and PC-3. The results showed that these compounds exhibited moderate to significant inhibitory effects on four tumor cell lines, among them compound 3d demonstrating the strongest activity, with IC₅₀ values of 8.3 ± 2.2 μmol/L and 9.1 ± 1.5 μmol/L for MCF-7 and PC-3 cells, respectively. Structure-activity relationship analysis revealed that the introduction of methyl and bromine atom in the meta position of phenyl was not conducive to the enhancement of anticancer activity, while the introduction of hydroxyl group in the para position was helpful to enhance the activity. When the phenyl was replaced by heterocyclic aromatic group, the anti-proliferative activity of the compound against MCF-7 and PC-3 decreased. Further molecular docking studies indicated that, except for compound 3i, all other compounds formed stable protein-ligand complexes with the target protein PARP-1 through hydrogen bonding and hydrophobic interactions. Compound 3d exhibited multiple interactions with PARP-1, and the hydrogen bond formed with the TYR907 residue was likely a key factor contributing to its significant antitumor activity.

Key words: Isopimaric acid, aroyl thiosemicarbazide, antitumor activity, molecular docking