

Synthesis and biological evaluation of phthalimide dithiocarbamate and dithioate derivatives as anti-proliferative and anti-angiogenic agents-I
Magdy Zahran (1)








(1) Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, 32511, Egypt
(2) Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, 32511, Egypt
(3) Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, 32511, Egypt
(4) Research and Development Department, Pharco B International Company for Pharmaceutical Industries, Borg El-Arab, Alexandria, 21934, Egypt
(5) Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, 32511, Egypt
(6) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo, 11599, Egypt
(7) Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, 32897, Egypt
(8) Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, 11599, Egypt
(*) Corresponding Author
Received: 15 Sep 2017 | Revised: 23 Oct 2017 | Accepted: 25 Oct 2017 | Published: 31 Dec 2017 | Issue Date: December 2017
Abstract
A facile synthesis of new phthalimide dithiocarbamate and dithioate analogs 8a-j, 9a-e and 9g-j were achieved by the reaction of N-chloromethyl and N-bromoethylphthalimide with carbon disulfide (CS2) and various amines. The structures of the synthesized analogs were elucidated by spectroscopic methods, including IR, 1H NMR and 13C NMR, and ESI-HRMS techniques. The antiproliferative activity of the newly synthesized compounds was also evaluated against various human cancer cell lines. The compound 9e and 9i exhibited the highest activity against human breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2 cells. Compound 8f showed better antiproliferative effect against colon carcinoma HCT-116 and cervical carcinoma HeLa compared to thalidomide. The binding affinity to vascular endothelial growth factor receptor (VEGFR) of some compounds was assessed in addition to molecular docking study. Compounds 9e and 9i showed high docking score values and they significantly declined the concentration of VEGFR.
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European Journal of Chemistry
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DOI: 10.5155/eurjchem.8.4.391-399.1652
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Funding information
Science and Technology Development Fund (STDF) through Project No. 3627 (Egyptian fund); Prof. Erik Pedersen, Department of Physics, Chemistry and Pharmacy, Nucleic Acid Center, University of Southern Denmark, Odense, Denmark.
Citations
[1]. El-Saied, El-Aarag, Salem, Said, Khalifa, El-Seedi
Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells
Molecules 24(18), 3313, 2019
DOI: 10.3390/molecules24183313

[2]. Marcel L. Almeida, Maria C.V.A. Oliveira, Ivan R. Pitta, Marina G.R. Pitta
Advances in Synthesis and Medicinal Applications of Compounds Derived from Phthalimide
Current Organic Synthesis 17(4), 252, 2020
DOI: 10.2174/1570179417666200325124712

[3]. Flaviana A. Santos, Marcel L. Almeida, Vitor A. S. Silva, Douglas C. F. Viana, Michelly C. Pereira, André S. L. Lucena, Maira G. R. Pitta, Marina R. Galdino-Pitta, Moacyr J. B. de Melo Rêgo, Ivan da Rocha Pitta
Synthesis and biological activities of new phthalimide and thiazolidine derivatives
Medicinal Chemistry Research 31(1), 108, 2022
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[4]. Ismail M. M. Othman, Mohamed A. M. Gad-Elkareem, Mohamed El-Naggar, Eman S. Nossier, Abd El-Galil E. Amr
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Journal of Enzyme Inhibition and Medicinal Chemistry 34(1), 1259, 2019
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[5]. Amira M. Gamal-Eldeen, Hussein S. Agwa, Magdy A.-H. Zahran, Bassem M. Raafat, Sherien M. El-Daly, Hamsa J. Banjer, Mazen M. Almehmadi, Afaf Alharthi, Nahed M. Hawsawi, Fayez Althobaiti, Mona A. M. Abo-Zeid
Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia
Frontiers in Chemistry 10, , 2022
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