Design, synthesis, molecular docking and cytotoxic activity of novel urea derivatives of 2-amino-3-carbomethoxythiophene
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J. Chem. Sci. (2020)132:126 https://doi.org/10.1007/s12039-020-01834-w
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Design, synthesis, molecular docking and cytotoxic activity of novel urea derivatives of 2-amino-3-carbomethoxythiophene VENUGOPALARAO VIKRAMa, SRINIVASA R PENUMUTCHUb, RAVIRAJ VANKAYALAc, SURESH THANGUDUd, KARTEEK RAO AMPERAYANIe and UMADEVI PARIMIe,* a Department
of Chemistry, GITAM University, Rushikonda, Visakhapatnam, India of Chemistry, Case Western Reserve University, Cleveland, OH, USA c Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, India d Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan e Department of Chemistry, Gayatri Vidya Parishad College for Degree and PG Courses (A), Rushikonda, Visakhapatnam, India E-mail: [email protected] b Department
MS received 20 November 2019; revised 29 January 2020; accepted 24 July 2020
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, 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. Keywords. One-pot synthesis; Urea derivatives; 2-Amino-3-carbomethoxythiophene; Cytotoxic activity; Docking study.
1. Introduction According to the World Health Organization (WHO), cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018 (https://www.who.int/news-room/fact-sheets/ detail/cancer). Therefore, there is a great demand to develop novel anticancer agents with higher efficacy and low toxicity. Ribonucleotide reductase (RR) is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides by de novo biosynthesis of DNA
precursors in nature an
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