Potential Anti-cancer Activity of Some Novel Isatin Sulfonamide Derivatives using HepG2 Cancer Cells

Abstract

The current study investigated the cytotoxic effect of ten newly synthesized isatin sulfonamide derivatives, following molecular hybridization, based on the association principle(s), on hepatocellular carcinoma (HCC) HepG2 and Huh7 cell lines, compared for safety using human normal retina pigmented epithelial (RPE-1) cells. The ten compounds showed variable in vitro cytotoxicity on both HepG2 and Huh7 cells, by using MTT cell viability assay. Four compounds were highly cytotoxic; however, 3 of them were of highest safety margin on RPE-1 cells in vitro as well as in vivo acute oral toxicity study (14-days). These later superior three compounds are (3a), (4b) and (4c) significantly decreased epithelial growth factor receptor (EGFR) level, and confirmed via performing molecular docking study. Having better and selective tyrosine kinase inhibitory potential towards EGFR more than erlotinib. Compounds 3a, 4b, and 4c inhibited Bcl-2, uPA, heparanase expression in cell lysate from HepG2-treated cells in comparison to doxorubicin-treated HepG2 cells (positive cytotoxic chemotherapeutic control). In conclusion, new isatin sulfonamides derivative compounds 3a, 4b and 4c showed variable potential on “hallmarks of cancer”, significant cytotoxic, anti-cancer activity, and apoptotic anti-angiogenic, anti-invasive, anti-proliferative, and anti-metastatic activities. In summary, compound “3a” is highly comparable to Dox. Regarding cell cycle G0-G1 phase % elongation, early and late apoptosis (tested by flow cytometry) and comparable to erlotinib regarding EGFR inhibition. Therefore, it could be pointed out in the current study that compound “3a” is the safest and active synthesized isatin sulfonamide derivative for HCC management.