Details

Autor(en) / Beteiligte

• Zhang, Qian
• Teng, Yuou
• Yuan, Yuan
• Ruan, Tingting
• Wang, Qi
• Gao, Xing
• Zhou, Yao
• Han, Kailin
• Yu, Peng
• Lu, Kui

Titel

Synthesis and cytotoxic studies of novel 5-phenylisatin derivatives and their anti-migration and anti-angiogenic evaluation

Ist Teil von

• European journal of medicinal chemistry, 2018-08, Vol.156, p.800-814

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• A number of 5-arylisatin derivatives were synthesized in 5–6 steps from readily available starting materials. Their structures were confirmed by 1H NMR and 13C NMR as well as LC/MS. The cytotoxicity of these novel isatins against human leukemia K562 cells were evaluated by MTT assay in vitro. SAR studies indicated that the N-substituted benzyl and C-5 substituted phenyl groups greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 present in the parent ring is required to maintain such a potency. Particularly, N-(p-methoxybenzyl)-5-(p-methoxyphenyl)isatin (compound 2m) showed the highest antitumor activity against K562 cell lines (IC50 = 0.03 μM). Moreover, treatment with compound 2m significantly inhibited liver cancer HepG2 cells proliferation and migration, which could also reduce the human umbilical vein endothelial cells (HUVEC) tube formation. In conclusion, compound 2m exhibited very good cancer cells proliferation inhibition by angiogenesis responses in vitro, and 2m might be a promising angiogenesis inhibitor for cancer treatment. A series of 5-arylisatin derivatives were synthesized. The cytotoxicity evaluation results revealed that the most potent compound 2m inhibit tumor cells proliferation by decreasing migration and angiogenesis. [Display omitted] •The antitumor SAR studies of novel 5-phenylisatin derivatives were performed.•The methoxyl groups of C-5 and N-substitution may enhance their cytotoxicy.•Compound 2m displayed the most potent cytotoxic activity (IC50 = 0.03 μM) against K562 cell lines.•2m inhibited the proliferation of tumor cells by decreasing migration and angiogenesis.