In the past few decades, thiourea derivatives have been intensively investigated as potential anticancer drugs. This class of compounds has been recognized as agents with promising inhibitory activity towards human lung adenocarcinoma cell lines, human breast cancer cells and human colorectal carcinoma. Antitumor activity of thiourea derivatives is based on potential inhibition of protein tyrosine kinases, topoisomerases, carbonic anhydrase and sirtuins.

Molecular docking analysis was performed on 20 newly designed thiourea derivatives of naproxen with potential antitumor activity, in order to propose their potential mechanisms of action. Designed derivatives contain amino acids, esters of amino acids and aromatic amines in the side chains. Crystal structures of different protein kinases involved in multidrug resistance were taken from the Protein Data Bank: 1M17 (EGFR), 3E87 (AKT2), 3HNG (VEGFR1) and 4JSV (mTOR).

The FRED 3.2.0.2 [9,10,11] and AutoDock Vina software were used for the analysis of binding of designed compounds into the active sites of the selected protein kinases. Analysis of binding poses in FRED software revealed the key binding interactions for derivatives 1 (with AKT2 and mTor) and 20 (with EGFR and VEGFR1). On the other hand, in AutoDock Vina, derivatives 16 and 17 formed key binding interactions with EGFR, AKT2 and VEGFR1. These 4 derivatives possess good molecular docking rankings in both docking software and represent potential anticancer candidates capable of fighting multidrug-resistant tumors.