New N-allylthiourea derivatives: Synthesis, molecular docking and <i>in vitro</i> cytotoxicity studies

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 (1 H-NMR), carbon nuclear magnetic resonence (13 C-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.

Anticancer evaluation of N-benzoyl-3-allylthiourea as potential antibreast cancer agent through enhances HER-2 expression

“…The uptake was read by ELISA reader at a wavelength of 570 nm and the absorbance results read were converted into the percentage of life. [ 14 20 ]…”

“…Furthermore, recent studies on allylthiourea derivatives showed the activity of these compounds against T47D and MCF-7 line breast cancer cells. [ 13 14 ] In this study, the activity of allylthiourea derivatives, namely N -benzoyl-3-allylthiourea (BATU) [ Figure 1 ], will be tested for the anticancer activity using MCF-7 cells with HER2 overexpression.…”

Rational Design, Synthesis and Cytotoxic Activity of N-(Phenylcarbamoyl)Benzamide on HeLa Cell Lines

“…This was to ensure that the predictions of the data were available when it was being developed as an anticancer drug candidate. Changes in ADMET Predictor's predictions after the new phenylurea derivative had been synthesized would certainly occur and they would be different from those for the mother compounds [13].…”

“…The next step was to verify the binding of the active compound with several amino acids associated with the hydrogen bonds and the steric interactions. The final stage was involved docking the compound using Molegro Virtual Docker, version 5.5 until the rerank scores (RS) were obtained [11,13,14].…”

“…The absorbance was higher when the cancer cells/normal cells were alive. Calculation of IC 50 was done by probit regression analysis using SPSS [13,20].…”