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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Synthesis of New Thioureas Derivatives and Evaluation of Their Efficacy as Proliferation Inhibitors in MCF-7 Breast Cancer Cells by Using 99mTc-MIBI Radiotracer

Author(s): Ahmad Hormati, Jafar Abbasi Shiran, Mikaeil Molazadeh, Babak Kaboudin* and Sajjad Ahmadpour*

Volume 17, Issue 7, 2021

Published on: 25 April, 2020

Page: [766 - 778] Pages: 13

DOI: 10.2174/1573406416666200425224921

Price: $65

Abstract

Background and Objectives: Anti-tumor activity of some thioureas derivatives is well documented in literature and received considerable attention. The present study aims to synthesize and characterize some novel thioureas and carbonylthioureas as anti-tumor agents for MCF-7 breast cancer cells in vitro and in vivo.

Materials and Methods: Several 1-allyl-3-(substituted phenyl), N,N'-(phenylene) bis(3- allyldithithiourea) and 1-cyclopropanecarbonyl-3-(substituted phenyl)-thioureas derivatives were synthesized and confirmed by FT-IR spectroscopy, NMR and 13C-NMR. Anti-tumor activity of these compounds was determined by various in vitro and in vivo assays including; MTT, tumor volume measurement as well as,99mTc-MIBI tumor uptake in MCF-7 tumor bearing nude mice.

Results: Among all of the synthesized compounds, some thioureas derivatives [3i] and [4b] at 100 nM concentration exhibited significant inhibitory effects on the proliferation of MCF-7 cell in vitro. However, this inhibition was not observed in HUVEC human endothelial normal cells. In vivo anti-tumor effects of the synthesized compounds on MCF-7 xenograft mouse models demonstrated a reduction in the tumor volume for various concentrations between 2 to 10 mg/kg after 21 days. These effects were comparable with Tamoxifen as standard anti-estrogen drug. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both [3i] and [4b] compounds at the maximum concentration (10 mg/kg) can lead to a significant decrease of 99mTc- MIBI tumor uptake.

Conclusion: Compounds [3i] and [4b] suppressed the growth of MCF-7 cells in the xenograft nude mice at the doses that were well-tolerated. Our study suggests that these new compounds with their significant anti-tumor effects, may serve as useful candidates for breast cancer therapy.

Keywords: Breast cancer, thiourea, NMR, MTT assay, biodistribution, MCF-7.

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