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      Novel HDAC/Tubulin Dual Inhibitor: Design, Synthesis and Docking Studies of α-Phthalimido-Chalcone Hybrids as Potential Anticancer Agents with Apoptosis-Inducing Activity

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          In order to develop novel anticancer HDAC/tubulin dual inhibitors, a novel series of α-phthalimido-substituted chalcones-based hybrids was synthesized and characterized by IR, 1H NMR, 13C NMR, mass spectroscopy and X-ray analysis.


          All the synthesized compounds were evaluated for their in vitro anticancer activity against MCF-7 and HepG2 human cancer cell lines using MTT assay. To explore the mechanism of action of the synthesized compounds, in vitro β-tubulin polymerization and HDAC 1 and 2 inhibitory activity were measured for the most potent anticancer hybrids. Further, cell cycle analysis was also evaluated.


          The trimethoxy derivative 7j showed the most potent anticancer activity, possessed the most potent β-tubulin polymerase and HDAC 1 and 2 inhibitory activity and efficiently induced cell cycle arrest at both G2/M and preG1phases in the MCF-7 cell line.

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          Most cited references 38

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          Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis.

           L Ouyang,  Z. Shi,  S. Zhao (2012)
          Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment. © 2012 Blackwell Publishing Ltd.
            • Record: found
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            Classification, Treatment Strategy, and Associated Drug Resistance in Breast Cancer.

            Breast cancer is the second leading cause of cancer death in women, affecting 1.7 million patients every year worldwide. As a result of its heterogeneous nature, the genetic profile and associated clinical feature varies greatly among different breast cancer subtypes. With the advancement of molecular biology, our understanding of breast cancer has improved greatly in recent years. In this review, we examine different types of breast cancer and summarize their clinical features, current treatment schemes, and potential drug resistance profiles in response to treatments. We believe that the understanding of the molecular mechanisms of each treatment and subsequent drug resistance development will eventually lead to the discovery of more effective and efficient second-line therapeutics.
              • Record: found
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              Histone deacetylase inhibitors: discovery and development as anticancer agents.

              Histone deacetylase (HDAC) inhibitors are a new class of targeted anticancer agents. Several HDAC inhibitors are in clinical trials and have shown significant activity against a spectrum of both haematological and solid tumours at doses that are well tolerated by patients. HDACs and histone acetyltransferases can, by reversible acetylation, modify the structure and function of histones and proteins in transcription factor complexes, which are involved in the regulation of gene expression, as well as many non-histone proteins that are involved in regulating cell proliferation and cell death. HDAC inhibitors are a structurally diverse group of molecules; these agents selectively alter the expression of genes. HDAC inhibitors can induce cancer cell death, whereas normal cells are relatively resistant to HDAC inhibitor-induced cell death.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                03 August 2020
                : 14
                : 3111-3130
                [1 ]Pharmacology and Toxicology Department, Faculty of Pharmacy, Port-Said University , Port-Said, Egypt
                [2 ]Medicinal Chemistry Department, Faculty of Pharmacy, Port-Said University , Port-Said, Egypt
                [3 ]Institute of Inorganic and Analytical Chemistry , Braunschweig, Germany
                Author notes
                Correspondence: Ahmed A E Mourad Tel +201069233766 Email ahmed.mourad@yahoo.com
                © 2020 Mourad et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 11, Tables: 7, References: 45, Pages: 20
                Original Research


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