Synthesis and Evaluation of the Cytotoxicity of a Series of ۱,۳,۴-Thiadiazole Based Compounds as Anticancer Agents

  • سال انتشار: 1392
  • محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 16، شماره: 11
  • کد COI اختصاصی: JR_IJBMS-16-11_002
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 224
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نویسندگان

Alireza Aliabadi

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

Elham Eghbalian

Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran ۲ Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

Amir Kiani

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

چکیده

  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 ۱,۳,۴-thiadiazole-derived compounds (۳a-۳l) were synthesized. N-(۵-Mercapto-۱,۳,۴-thiadiazol-۲-yl)-۲-(۴-methoxyphenyl) acetamide (۲) was prepared through direct amidation of ۴-methoxyphenylacetic acid (۲) with ۵-amino-۱,۳,۴-thiadiazole-۲-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 ۲ to prepare compounds ۳a-۳l. In vitro cytotoxicity assessment using MTT method was applied and results are presented as IC۵۰. Results: All the synthesized compounds were characterized by ۱H-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 (۳a-۳l) demonstrated a higher cytotoxic activity against MDA-MB-۲۳۱ breast cancer cell line in comparison with other cell lines. Conclusion: It is notable that four synthesized compounds ۳h (IC۵۰= ۱۱ ± ۰.۱۸ μM), ۳j (IC۵۰= ۱۰ ± ۰.۳۹ μM), ۳k (IC۵۰= ۱۱ ± ۰.۷۷ μM) and ۳l (IC۵۰= ۸ ± ۰.۶۹ μM) exhibited higher cytotoxic activity against MDA-MB-۲۳۱ cell line compared to imatinib (IC۵۰= ۲۰ ± ۰.۶۹ μM) as the reference drug.

کلیدواژه ها

Anticancer Cytotoxicity Synthesis ۱, ۳, ۴-Thiadiazole

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