Synthesis and Evaluation of the Cytotoxicity of a Series of 1,3,4-Thiadiazole Based Compounds as Anticancer Agents

Document Type : Original Article

Authors

1 Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

2 Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran 2 Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

3 Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

 




Objective(s):
Nowadays, cancer is an important public health problem in all countries. Limitations of current chemotherapy for neoplastic diseases such as severe adverse reactions and tumor resistance to the chemotherapeutic drugs have been led to a temptation for focusing on the discovery and development of new compounds with potential anticancer activity.
 
Materials and Methods:
A new series of 1,3,4-thiadiazole-derived compounds (3a-3l) were synthesized. N-(5-Mercapto-1,3,4-thiadiazol-2-yl)-2-(4-methoxyphenyl) acetamide (2) was prepared through direct amidation of 4-methoxyphenylacetic acid (2) with 5-amino-1,3,4-thiadiazole-2-thiol using EDC (N-Ethyl-N-dimethylaminopropyl carbodiimide) and HOBt (Hydroxybenzotriazole). Then, various derivatives of benzyl chloride containing electron withdrawing and electron donating moieties were reacted with compound 2 to prepare compounds 3a-3l. In vitro cytotoxicity assessment using MTT method was applied and results are presented as IC50.
Results:
All the synthesized compounds were characterized by 1H-NMR and IR spectroscopy. Some of the synthesized compounds were also characterized using MS spectroscopy. Related melting points were also recorded. According to the obtained data from MTT assay, all compounds (3a-3l) demonstrated a higher cytotoxic activity against MDA-MB-231 breast cancer cell line in comparison with other cell lines.
Conclusion:
It is notable that four synthesized compounds 3h (IC50= 11 ± 0.18 μM), 3j (IC50= 10 ± 0.39 μM), 3k (IC50= 11 ± 0.77 μM) and 3l (IC50= 8 ± 0.69 μM) exhibited higher cytotoxic activity against MDA-MB-231 cell line compared to imatinib (IC50= 20 ± 0.69 μM) as the reference drug.

Keywords

References

 
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Iranian Journal of Basic Medical Sciences
Volume 16, Issue 11 - Serial Number 11
November 2013
Pages 1133-1138

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