LAUSR

Abstract An efficient feasible route for the one-pot synthesis of novel series of urea derivatives (2a–2j) from 2-amino-3-carbomethoxythiophene (1) via in situ isocyanate has been developed, and their corresponding anticancer activities were accomplished. The series of urea derivatives were characterized by using 1 H, 13 C nuclear magnetic resonance and mass spectroscopic analysis. The cytotoxic activities were evaluated against human cervical (HeLa) and human lung (NCI-H23) cancer cell lines. These studies revealed satisfactory activity for some of the compounds, which could potentially serve as lead compounds for drug discovery and development. Furthermore, molecular docking studies supported in identifying the potential binding sites between the urea derivatives and eukaryotic ribonucleotidereductase (RR). High ambiguity driven docking (HADDOCK) modelling was specifically employed to determine the model complex of RR and urea derivatives. The proposed model has provided a deep insight into the molecular level interactions of RR-urea model complexes in understanding the exact pharmacophore for designing highly potent RR inhibitors. Overall, the present work has shed light in developing a feasible and robust approach for the synthesis of novel urea derivatives of 2-amino-3-carbomethoxythiophene and identified a part of molecular structure that is responsible for a specific biological interaction leading to potential anticancer activities. Graphic abstract We report herein, the experimental design, synthesis and characterization of a novel series of urea derivatives of 2-amino-3carbomethoxythiophene with pyrimidine amine and benzyl amine analogues as both derivatives which exhibited potential antitumor activity via one pot synthesis and subsequently studied the structure activity relationships (SAR), and anticancer activities. The docking studies identified a part of molecularstructure that is responsible for a specific biological interaction leading to the destruction of cancer cells.