Synthesis,cytotoxic activity,and tubulin polymerization inhibitory activity of new pyrrol-2(3H)-ones and pyridazin-3(2H)-ones |
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| Affiliation: | 1. Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;2. Department of Pharmaceutical Chemistry, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia;3. Cancer Biology Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Dokki, Giza, Egypt;1. School of Biological Engineering, Tianjin University of Science and Technology, #29, 13th Avenue, TEDA, Tianjin 300457, China;2. Tianjin Binjiang Pharma, Inc., #238 Baidi Road, Nankai District, Tianjin 300192, China;3. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, #238 Baidi Road, Nankai District, Tianjin 300192, China;1. Dept. of Chemistry, Government Arts College, Coimbatore, 641018, Tamil Nadu, India;2. Dept. of Biotech, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India;1. Suez University, Faculty of Science, Chemistry Department, 43518, Suez, Egypt;2. Suez University, Faculty of Petroleum and Mining Engineering, Science and Mathematics Department, Suez, Egypt;1. Department of Chemical Sciences, Ariel University, Ariel, Israel;2. Department of Molecular Biology, Ariel University, Ariel, Israel;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey;2. Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey;3. Department of Medical Genetics, School of Medicine, Baskent University, Adana, Turkey |
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| Abstract: | A series of new pyrrol-2(3H)-ones 4a-f and pyridazin-3(2H)-ones 7a-f were synthesized and characterized using different spectroscopic tools. Some of the tested compounds revealed moderate activity against 60 cell lines. The E form of the pyrrolones 4 showed good cytotoxic activity than both the Z form and the corresponding open amide form. Furthermore, the in vitro cytotoxic activity against HepG2 and MCF-7 cell lines revealed that compounds (E)4b, 6f and 7f showed good cytotoxic activity against HepG2 with IC50 values of 11.47, 7.11 and 14.80 μM, respectively. Compounds (E)4b, 6f, 7d and 7f showed a pronounced inhibitory effect against cellular localization of tubulin. Flow cytometric analysis indicated that HepG2 cells treated with (E)4b showed a predominated growth arrest at the S-phase compared to that of G2/M-phase. Molecular modeling study using MOE® program indicated that most of the target compounds showed good binding of β-subunit of tubulin with the binding free energy (dG) values about −10 kcal/mole. |
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| Keywords: | Pyrrolone Pyridazinone Cytotoxicity Tubulin Immunofluorescence Docking study |
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