Email this article In Vitro Antitumor Activity of Newly Synthesized Pyridazin-3(2H)-One Derivatives via Apoptosis Induction
- Authors: Bouchmaa N.1,2, Tilaoui M.2, Boukharsa Y.1, Jaâfari A.2, Mouse H.A.2, Ali Oukerrou M.2, Taoufik J.1, Ansar M.1, Zyad A.2
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Affiliations:
- Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University
- Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
- Issue: Vol 51, No 10 (2018)
- Pages: 893-901
- Section: Article
- URL: https://journals.rcsi.science/0091-150X/article/view/244846
- DOI: https://doi.org/10.1007/s11094-018-1712-x
- ID: 244846
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Abstract
Systemic toxicity associated with drug resistance continues to be the major obstacle to curative therapy of cancer. Tumor cell resistance to chemotherapeutic drugs often results in coordinate resistance to other structurally and functionally unrelated drugs and the subsequent development of cross resistance phenotype. Therefore, it seems necessary to identify new molecules as anticancer agents. In this process, we synthesized a series of new pyridazin-3(2H)-one derivatives and evaluated their antitumor potential. These cyclic molecules were synthesized and designed as a combination of benzofuran with pyridazinones. All final compounds have been characterized by spectral and elemental analyses to confirm successful synthesis reactions. To evaluate their anticancer activity, all derivatives were assessed against the human breast adenocarcinoma cell line (MCF-7) and the murine mastocytoma cell line (P815) using the methyl tetrazolium Test (MTT assay). The cytotoxic activity was found to be dose-dependent and the IC50 values of the synthesized compounds ranged from 14.5 to 40 μM against MCF-7 and from 35 to 82.5 μM against P815. At the same time, no cytotoxic activity was observed against normal cells. In order to investigate the molecular mechanism of the most cytotoxic product (6f), apoptosis induction was measured against MCF-7 cells. Using the annexin-V FITC staining technique, we showed that the cytotoxic effect of this product is associated with apoptosis induction.
About the authors
Najat Bouchmaa
Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University; Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
Email: ab.zyad2@gmail.com
Morocco, Rabat; Beni-Mellal
Mounir Tilaoui
Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
Email: ab.zyad2@gmail.com
Morocco, Beni-Mellal
Youness Boukharsa
Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University
Email: ab.zyad2@gmail.com
Morocco, Rabat
Abdessalam Jaâfari
Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
Email: ab.zyad2@gmail.com
Morocco, Beni-Mellal
Hassan Aît Mouse
Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
Email: ab.zyad2@gmail.com
Morocco, Beni-Mellal
My. Ali Oukerrou
Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
Email: ab.zyad2@gmail.com
Morocco, Beni-Mellal
Jamal Taoufik
Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University
Email: ab.zyad2@gmail.com
Morocco, Rabat
M’hammed Ansar
Laboratory of Medicinal Chemistry, Faculty of Medicine and Pharmacy, Mohammed V University
Email: ab.zyad2@gmail.com
Morocco, Rabat
Abdelmajid Zyad
Laboratory of Biological Engineering, Natural Substances, Team of Cellular and Molecular Immuno-Pharmacology, Immunobiology of Cancer Cells, Faculty of Sciences and Technologies, Sultan Moulay Slimane University
Author for correspondence.
Email: ab.zyad2@gmail.com
Morocco, Beni-Mellal
