Ahmad Hormati, Jafar Abbasi Shiran, Mikaeil Molazadeh, Babak Kaboudin* and Sajjad Ahmadpour* Pages 766 - 778 ( 13 )
Background & Objective: 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 & 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.
Breast cancer, Thiourea, NMR, MTT assay, Biodistribution, MCF-7.
Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom, Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Department of Medical Physics, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Gastroenterology and Hepatology Diseases Research Center, Qom University of Medical Sciences, Qom