Recyclization and biological activity of thiocyanatoacetamides containing a thieno[2,3-b]quinoline fragment

Thiocyanatoacetamides incorporating a thieno[2,3-b]quinoline fragment represent highly reactive bifunctional derivatives. The combination of an electrophilic carbonyl center and the thiocyanate group (-SCN) at the α-carbon atom makes them valuable intermediates for constructing polyfunctional sulfur- and nitrogen-containing heterocycles. Furthermore, these compounds exhibit a wide spectrum of biological activities, including antitubercular, antitumor, fungicidal, antibacterial, and neurotropic effects.

The synthesis of the target compounds was achieved via a domino reaction of chloroacetamides with potassium thiocyanate, leading to the formation of polycondensed pyridothienopyrimidines. In this study, 8 novel representatives were synthesized for the first time. Their structures were fully characterized by IR spectrophotometry and ¹H and ¹³C NMR spectroscopy. A computational prediction of potential protein targets was performed using molecular docking (Galaxy Web Sagittarius). The agrochemical potential was evaluated experimentally against the herbicide 2,4-D on plant models.

Molecular docking studies revealed that the synthesized compounds are capable of binding to the active site of the Keap1 protein, a well-known sensor of oxidative stress, as well as exhibiting complementary interactions with the AMPA receptor GluR2, a central nervous system receptor involved in excitatory signal transmission. Furthermore, an experimental evaluation of the agrochemical potential against the herbicide 2,4-D was performed, demonstrating that the target molecules exhibit significant activity as potential antidotes and plant growth regulators.