Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

New N-allylthiourea derivatives: Synthesis, molecular docking and in vitro cytotoxicity studies

Tri Widiandani¹ , Siswandono ¹, Edy Meiyanto², Melanny Ika Sulistyowaty^1,3, Bambang Tri Purwanto¹, Suko Hardjono¹

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Airlangga, Surabaya; ²Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia; ³Graduate School in Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

For correspondence:- Tri Widiandani Email: tri-w@ff.unair.ac.id Tel:+6281803022660

Accepted: 26 July 2018 Published: 31 August 2018

Citation: Widiandani T, S, Meiyanto E, Sulistyowaty MI, Purwanto BT, Hardjono S. New N-allylthiourea derivatives: Synthesis, molecular docking and in vitro cytotoxicity studies. Trop J Pharm Res 2018; 17(8):1607-1613 doi: 10.4314/tjpr.v17i8.20

© 2018 The authors.
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Abstract

Purpose: To synthesise derivatives of N-allylthiourea and evaluate their anticancer activities against epidermal growth factor receptor (EGFR) using in silico and in vitro methods.

Methods: Four compounds were synthesized using the Schotten-Baumann reaction. The structures of the synthesized compounds were confirmed using infrared (IR), proton nuclear magnetic resonance (¹H-NMR), carbon nuclear magnetic resonence (¹³C-NMR) and electrospray ionization mass spectrometry (ESI-MS) methods. Molecular modeling was carried out with Molegro Virtual Docker version 5.5 through docking of the compounds onto the protein binding site of EGFR, with protein data bank (PBD) codes 1M17, 1XKK, and 3POZ. In vitro cytotoxicity was evaluated in MCF-7 cell lines using MTT assay.

Results: The synthesized compounds showed lower Rerank Scores, relative to N-allylthiourea and hydroxyurea. The low Rerank Score values implied stable molecular bonds, and hence higher biological activities. In addition, the derivatives showed cytotoxicities against MCF-7 cell line (IC₅₀: 0.21 – 0.38 mM) which were superior to those of N-allylthiourea (IC₅₀: 5.22 mM) and hydroxyurea (IC₅₀: 2.89 mM).

Conclusion: The predicted anticancer activities of the synthesized compounds are consistent with results from in silico studies and assays of cytotoxicity against MCF-7 cell lines. Thus, N-allylthiourea derivatives can potentially be developed as anticancer drugs

Keywords: N-allylthiourea derivatives, In silico, Synthesis, Cytotoxicity, MCF-7, EGFR