Synthesis of Semaxanib-like 3-alkylideneoxindoles and their binding investigation with ctDNA by multiple methods

Compounds with 3-alkylideneoxindole units are common seen in natural products, medicines and active molecules. Here, three Semaxanib-like 3-alkylideneoxindole derivatives were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, HRMS and FT-IR. And their binding information with ctDNA were investigated by multiple methods including UV spectroscopy, fluorescence spectroscopy, ¹H NMR, viscometric method and MOE-docking. Fluorescence competition experiments reflected that all of these compounds bound to the groove region of ctDNA with the binding constants 10⁴ by orders of magnitude. Minor alterations were observed from viscometric method, which also indicated that all compounds interacted with ctDNA in a grooved manner. UV spectroscopy and ¹H NMR further proved the above conclusion. Furthermore, MOE docking provided visualization of the binding results, and demonstrated that hydrogen bonds play a crucial role in the binding between the three compounds and ctDNA. This study offered detailed information about 3-alkylideneoxindole compounds binding to ctDNA, and provided valuable reference for more fully developing of drugs with 3-alkylideneoxindole units.