Synthesis of Melphalan and Parthenolide hybride and Investigation of Their Cytotoxicity Activity Against Breast Cancer

Document Type : Original Article


1 Department of medicinal chemistry, Pharmacy faculty

2 Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

3 medicinal Chemistry, Medicinal Faculty

4 department of Biology, Faculty of Science, Islamic Azad University of Mashhad, IRAN.


Background and Objective: Melphalan is a chemotherapy agent and used for treating of metastatic melanoma and breast cancer. However, the side effect of this compound have been limited its clinical care. Parthenolide, a sesquiterpene lactone is a bioactive compound from Tanacetum parthenium medicinal plant and have anti-leukemia properties. Despite the many advantages of sesquiterpene terpene lactones, these compounds have two obvious drawbacks: non-specificity for cancer cells and low solubility in water. Therefore, the aim of this study is to synthesis of melphalan and parthenolide hybride using conjugation method to enhance the higher potency to anticancer drug. Meanwhile, the cytotoxicity activity of this compound has been tested against breast cancer cell line (MDA-MB-231).
Subjects and Methods: In order to synthesis of mentioned compound, the melphalan as an anticancer drug have been conjugated to parthenolide sesquiterpene lactone by aza-Michael reaction. Then, the cytotoxicity activity of this compounds have been tested by alamar blue assay.
Results: The parthalan product synthesis of melphalan anticancer drug and parthenolide sesquiterpene have been analysed and identified by LC-MS. The cytotoxicity activity results indicated that cell viability of cancer cell (MDA-MB-231) have been decreased in dose dependent manner and the IC50 of parthalan, parthenolide and synthesized hybrid were reported with respective values of 13/5, 24 and 23 μg/ml.
Conclusion: The overall results of this research demonstrated that parthenolide-melphalan hybrid induce significantly enhanced the higher potency of parthenolide.


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