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 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.

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.

中文翻译：

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2-氨基-3-羰基甲氧基噻吩新型脲衍生物的设计，合成，分子对接和细胞毒活性

摘要

已经开发了一种通过原位异氰酸酯一锅合成2-氨基-3-羰基甲氧基噻吩（1）合成一系列新的尿素衍生物（2a-2j）的有效途径，并实现了其相应的抗癌活性。该系列尿素衍生物的特征是使用¹ H，¹³C核磁共振和质谱分析。评估了针对人宫颈癌（HeLa）和人肺癌（NCI-H23）癌细胞系的细胞毒活性。这些研究表明某些化合物具有令人满意的活性，可以潜在地用作药物发现和开发的先导化合物。此外，分子对接研究支持确定尿素衍生物和真核生物核糖核苷酸还原酶（RR）之间的潜在结合位点。高歧义驱动对接（HADDOCK）建模专门用于确定RR和尿素衍生物的模型复杂度。所提出的模型为理解RR-脲模型复合物的分子水平相互作用提供了深刻的见解，以了解设计高效RR抑制剂的确切药效基团。总体，

图形摘要

我们在这里报告了2-氨基-3羰基甲氧基噻吩的新型系列尿素衍生物的实验设计，合成和表征，其中嘧啶胺和苄基胺类似物均为这两种衍生物，它们通过一个锅合成显示出潜在的抗肿瘤活性，随后研究了结构活性关系（SAR）和抗癌活动。对接研究确定了分子结构的一部分，该部分负责导致癌细胞破坏的特定生物相互作用。