Synthesis, screening and pro-apoptotic activity of novel acyl spermidine derivatives on human cancer cell lines

The polyamines putrescine, spermidine, and spermine are polycationic, alkyl polyamines which play a significant role in eukaryotic cell proliferation. The polyamine metabolism and function are dysregulated in tumor cells making them an attractive therapeutic target by employing polyamine analogs. These analogs have a high degree of similarity with the structure of polyamines but not with their function. Multidrug resistance is a major factor in the failure of many chemotherapeutic drugs which necessitates further research and exploration of better novel alternatives. In the present study, Twenty-six novel acylspermidine derivatives were synthesized and evaluated for their anti-proliferative and pro-apoptotic activities on human breast cancer cells and T-lymphoblastic leukemia cells. The cell proliferation and apoptosis assays using WST-1 and annexin-V/7AAD staining respectively suggest that Compound 1 (C19H41N3O2), Compound 7(C25H51N3O2) and Compound 8 (C29H59N3O) significantly reduced cancer cell viability in a dose-and time-dependent manner. Interestingly, compounds 7, 8 and 9 had slight or no effect on cell proliferation of non-cancerous cells. These studies speculate that these novel acylspermidine derivatives could be promising candidates in designing an anti-proliferative drug, targeting both solid and blood cancer cells. (C) 2017 Elsevier Masson SAS. All rights reserved.