Synthesis Of Novel Urea Derivatives Research Articles

Cysteine protease domain of potato virus Y: The potential target for urea derivatives

The cysteine protease structural domain (CPD) encoded by the potato virus Y (PVY) accessory component protein helper component-proteinase (HC-Pro) is an auxiliary component of aphid virus transmission and plays an important role in virus infection and replication. Urea derivatives have potential antiviral activities. In this study, the PVY HC-Pro C-terminal truncated recombinant protein (residues 307–465) was expressed and purified. The interactions of PVY CPD with urea derivatives HD1–36 were investigated. Microscale thermophoresis experiments showed that HD6, −19, −21 and − 25 had the strongest binding forces to proteins, with Kd values of 2.16, 1.40, 1.97 and 1.12 μM, respectively. An experiment verified the microscale thermophoresis results, and the results were as expected, with Kd values of 6.10, 4.78, 5.32, and 4.52 μM for HD6, −19, −21, and − 25, respectively. Molecular docking studies indicated that the interaction sites between PVY CPD and HD6, −19, −21, and − 25, independently, were aspartic acid 121, asparagine 48, and tyrosine 38, which played important roles in their binding. In vivo experiments verified that HD25 inhibited PVY more than the control agents ningnanmycin and urea. These data have important implications for the design and synthesis of novel urea derivatives.

Design and synthesis of novel urea derivatives of pyrimidine-pyrazoles as anticancer agents

Designed and synthesized a series of novel urea derivatives of pyrimidine-pyrazole, and screened for their anticancer activity. Compounds with (3,5-dinitro and 3,4,5-trimethoxy) substitution were exhibited more potent cytotoxicity than standard Etoposide. Molecular docking studies suggested that compounds were well occupied at the colchicine binding site and interacted with α, β-tubuline interface of x-ray crystal structure of (PDB:1SA0), which demonstrates that synthesized compounds are promising tubulin inhibitors.

Design, synthesis, molecular docking and cytotoxic activity of novel urea derivatives of 2-amino-3-carbomethoxythiophene

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 1H, 13C 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. 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.