Triazene salts: Design synthesis ctDNA interaction lipophilicity determination DFT calculation and antiproliferative activity against human cancer cell lines

摘要

Synthesis, characterization and investigation of antiproliferative activity of nine triazene salts against human cancer cells lines (MV-4-11, MCF-7, JURKAT, HT-29, Hep-G2, HeLa, Du-145 and DAUDI), and normal human mammary epithelial cell line (MCF7-10A) is presented. The structures of novel compounds were determined using ¹H and ¹³C NMR, and GC-APCI-MS analyses. Among the derivatives, compound >2c, >2d, >2e and >2f has very strong activity against biphenotypic B myelomonocytic leukemia MV4-11, with IC50 values from 5.42 to 7.69 µg/ml. The cytotoxic activity of compounds >2c->2f against normal human mammary gland epithelial cells MCF-10A is 6–11 times lower than against cancer cell lines. Our results also show that compounds >2c and >2f have very strong activity against DAUDI and HT-29 with IC50 4.91 µg/ml and 5.59 µg/ml, respectively. Their lipophilicity was determined using reversed-phase ultra-performance liquid chromatography and correlated with antiproliferative activity. Our UV–Vis spectroscopic results indicate also that triazene salts tends to interact with negatively charged DNA phosphate chain. To support the experiment, theoretical calculations of the ¹H NMR shifts were carried out within the Density Functional Theory.