Synthesis of Novel Pyrazole Derivatives Containing Isatins as Potential Apoptosis Inducer in Non-small Lung Cancer A549 Cells

Abstract

Two kinds of novel pyrazole derivatives containing isatins, total of 12 target compounds, were prepared from 4-hydroxyacetophenone via addition, cyclization, substitution, hydrazinolysis and condensation, which were characterized by 1 H NMR, 13 C NMR and HRMS. The anti-neoplastic activity of target molecules was evaluated against human non-small cell lung cancer cell line A549 using cell counting Kit-8 (CCK-8) assay. The data showed that several compounds possessed potential anticancer effect. Among them, N'-(3-imino-6-chloroindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7e) and N'-(3-imino-6-bromoindole-2-one)-1-benzyl-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide (7f) exhibited IC 50 values of 30.41 and 29.69 μmol/L, respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells, reduce the mitochondrial membrane potential, but have no effect on the cell cycle. Those data indicated that the anti-proliferative activity of molecule 7f was mediated by apoptosis-dependent mechanism involving the mitochondrial pathway in A549 cells.

Recent advances in isatin hybrids as potential anticancer agents

“…The isatin–pyrazole hybrids 27a,b (IC 50 : 30.41 and 29.69 μM, CCK‐8 assay) and 28 (IC 50 : 58.48 μM) were active against A549 cancer cells and the SAR proved that introduction of halogen atoms into C‐6 position of isatin moiety could improve the activity. [ 82 ] The mechanism study indicated that hybrid 27b had the ability to induce apoptosis of A549 cells, reduce the mitochondrial membrane potential, but its activity was lower than that of cisplatin (IC 50 : 8.18 μM).…”