Synthesis and high antiproliferative activity of dehydroabietylamine pyridine derivatives in vitro and in vivo

Several bioactive dehydroabietylamine Schiff-bases (L¹−L⁴), amides (L⁵−L¹¹) and complex CuL³(NO₃)₂, Cu(L⁵)₃, Co(L⁶)₂Cl₂ had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L⁰). For HepG2 cells, L¹, L² and L³ had higher anti-HepG2 activity, especially L¹ (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L¹, L², L³ and L⁴ had higher anti-MCF-7 activity, especially L³(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L² and L³ had higher anti-A549 activity. Furthermore, L¹ and L³ may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L¹, L² and L³ could induce apoptosis through intercalating into DNA.