Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity

Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic... Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and their Cu(II) complexes were designed, synthesized and analysed using spectral and analytical techniques. The analytical results indicated the formation of the complexes in 1:1 or 1:2 (Metal:Ligand) ratio. The geometry around the Cu centers was confirmed to be tetrahedral or octahedral. The cytotoxic activity of the new compounds was evaluated using MCF-7 (human breast adenocarcinoma), A2780 (human ovary adenocarcinoma) and HT29 (human colon adenocarcinoma), in addition to MRC5 (normal human fetal lung fibroblast) cells using the MTT cytotoxicity assay. The Schiff base 12c and the Cu complex 13b were the most active in the two series with IC50 values in the range of 0.14–2.54 μM against the three cell lines. Also, the Cu complex 13e showed excellent activity against HT29 with IC50 = 0.05μM. 7-Cyano-N-(4-methoxyphenyl)-6-((3-phenylallylidene) amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (12c) showed high selectivity (6–13 folds) for cancerous cells over normal cells; and it induced marginal increases in the G1 and S phases of MCF-7 cells during cell cycle analysis, while compound 13b increased the MCF-7 Sub-G1 proapoptotic population, and blocked cells in the G2-M phase in a dose dependent manner. The annexin V apoptosis assay revealed the ability of compounds 12c and 13b to increase the early apoptotic MCF-7 cell populations two and three fold, respectively. Furthermore, these findings were supported by data showing that the two compounds (12c and 13b) elicit cytotoxic activity. Taken together, the data presented in this study warrants further in vitro and in vivo investigations. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity

Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity

European Journal of Medicinal Chemistry 145 (2018) 350e359 Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech Research paper Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis and cytotoxic screening with potential apoptosis-inducing activity a, b c, d d, e Ahmed M. Gouda , Hoda A. El-Ghamry , Tahani M. Bawazeer , f, * g, h i Thoraya A. Farghaly , Ashraf N. Abdalla , Akhmed Aslam Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt Chemistry Department, Faculty of Applied Science, Umm AleQura University, Makkah, Saudi Arabia Medical Applications of Nanobiotechnology Research Group, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia Department of Chemistry Faculty of Science, Cairo University, Giza, Egypt Department of Pharmacology and Toxicology, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia Department of Pharmacology, Medicinal and Aromatic Plants Research Institute, National Center for Research, Khartoum 2404, Sudan Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia article i nf o abstract Article history: Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and their Cu(II) complexes Received 23 November 2017 were designed, synthesized and analysed using spectral and analytical techniques. The analytical results Received in revised form indicated the formation of the complexes in 1:1 or 1:2 (Metal:Ligand) ratio. The geometry around the Cu 1 January 2018 centers was confirmed to be tetrahedral or octahedral. The cytotoxic activity of the new compounds was Accepted 4...
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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Masson SAS
ISSN
0223-5234
eISSN
1768-3254
D.O.I.
10.1016/j.ejmech.2018.01.009
Publisher site
See Article on Publisher Site

Abstract

Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and their Cu(II) complexes were designed, synthesized and analysed using spectral and analytical techniques. The analytical results indicated the formation of the complexes in 1:1 or 1:2 (Metal:Ligand) ratio. The geometry around the Cu centers was confirmed to be tetrahedral or octahedral. The cytotoxic activity of the new compounds was evaluated using MCF-7 (human breast adenocarcinoma), A2780 (human ovary adenocarcinoma) and HT29 (human colon adenocarcinoma), in addition to MRC5 (normal human fetal lung fibroblast) cells using the MTT cytotoxicity assay. The Schiff base 12c and the Cu complex 13b were the most active in the two series with IC50 values in the range of 0.14–2.54 μM against the three cell lines. Also, the Cu complex 13e showed excellent activity against HT29 with IC50 = 0.05μM. 7-Cyano-N-(4-methoxyphenyl)-6-((3-phenylallylidene) amino)-2,3-dihydro-1H-pyrrolizine-5-carboxamide (12c) showed high selectivity (6–13 folds) for cancerous cells over normal cells; and it induced marginal increases in the G1 and S phases of MCF-7 cells during cell cycle analysis, while compound 13b increased the MCF-7 Sub-G1 proapoptotic population, and blocked cells in the G2-M phase in a dose dependent manner. The annexin V apoptosis assay revealed the ability of compounds 12c and 13b to increase the early apoptotic MCF-7 cell populations two and three fold, respectively. Furthermore, these findings were supported by data showing that the two compounds (12c and 13b) elicit cytotoxic activity. Taken together, the data presented in this study warrants further in vitro and in vivo investigations.

Journal

European Journal of Medicinal ChemistryElsevier

Published: Feb 10, 2018

References

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