Experimental and theoretical insights about the effect of some newly designed azomethine group‐contained macroheterocycles on oxidative stress and DNA repair gene profiles in neuroblastoma cell lines

Abstract

We report herein the synthesis of new azomethine group containing forty-, sixty-eight- and seventy-two-membered macroheterocyclic compounds and the investigation of their activity against the neuroblastoma cell line. The synthesis of targeted compounds was done by condensation of dialdehydes with polyamines and their structures were investigated by 1H and 13C NMR and MALDI MS methods. Anticancer activity of these newly synthesized molecules was studied in the neuroblastoma (SH-SY5Y) cell line at eight different concentrations (1–100 µg/ml) for 24 h, 48 ​​hrs and 72 h by MTT method. In addition to it, oxidative stress (GPX1, PRDX1, CAT, SOD1, NQO1) and DNA repair (ATR, ERCC1, CDKN1A, PRKDC) gene profiles were also investigated by RT-PCR method. It was found that all synthesized compounds showed the highest activity after 72 h of incubation. PRDX1 gene expression in the case of all investigated compounds was found to be higher than the control group, whereas ABCB1 (MDR) gene expression increased only in the case of molecule 1. Results also demonstrate that the expression levels of GPX and SOD1 genes were high in the case of molecule 2, whereas molecule 1 manifested low expression levels of ERCC1, ATR, CDKN1A, PRKDC, GPX1, ABCB1(MDR), CAT, SOD1 and NQO1 genes. Along with experimental studies, theoretical studies were also carried out. The String v11 program was used to determine the interaction of proteins involved in oxidative stress and DNA repair mechanisms with other proteins. The results of the molecular docking analysis were found to be in good agreement with the experiments.