Purpose: Cancer as one of the major diseases with high mortality rates threats human life in the world. Subsequently, the design new potent anticancer agents has attracted much attention in the area of synthetic and medicinal chemistry. In this study, new triazol-linked spiroindolinequinazolinone, thiazol-oxindole and oxindole-thiosemicarbazone conjugates were synthesized and evaluated for their in vitro cytotoxic activity toward different cancer lines.
Methods: Some new triazol-linked oxindoles and spirooxindoles conjugates were synthesized. The synthesized compounds were tested for their in vitro cytotoxic activity toward cancer lines including A375, PC3, LNCaP, MDA MB231 and normal cells HDF (human dermal fibroblast).
Results: Among all synthesized compounds, the triazol-linked oxindol-thiosemicarbazone conjugate 10b showed the highest cytotoxic activity against different cancer cells. By using quantitative real time PCR (qRT-PCR), it was found that 10b is able to induce apoptosis by alteration of Bax, Bcl2 balance (i.e. by up regulation of Bax and down regulation of Bcl-2 mRNA expression levels). The DAPI staining was used to show the death of cancer cells in the presence of 10b. Interestingly, 10b suppressed the migration of LNCaP cancer cells by up-regulation of epithelial markers (E-cadherin) and down-regulation of mesenchymal markers (vimentin).
Conclusion: Our findings revealed that the compound 10b may be a new potent candidate with multiple biological activities to design therapeutic agents against different cancers. Synthesis and evaluation of in vitro cytotoxic effects of triazol/spiroindolinequinazolinedione, triazol/indolin-3-thiosemicarbazone and triazol/thiazol-indolin-2-one conjugates.
Keywords: Anticancer activity; Apoptosis; Isatin; Oxindole containing thiazole; Spiroindolinequinazoline-dione; Spirooxindole containing triazole.