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Open AccessArticle

Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors

1
Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2
Applied Organic Chemistry Department, National Research Centre, 12622 Dokki, Giza, Egypt
3
Department of Peptide Chemistry, National Research Centre, 12622 Dokki, Giza, Egypt
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, 11754 Cairo, Egypt
5
Bioproducts Research Department, Zoology Department, Faculty of Science, King Saud University, Riyadh 11451, Saudi Arabia
6
Chemistry of Natural and Microbial Products Department, National Research Centre, 12622 Dokki, Cairo, Egypt
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(10), 2416; https://doi.org/10.3390/molecules23102416
Received: 5 September 2018 / Revised: 17 September 2018 / Accepted: 18 September 2018 / Published: 20 September 2018
A series of macrocyclic pyrido-pentapeptide candidates 26 were synthesized by using N,N-bis-[1-carboxy-2-(benzyl)]-2,6-(diaminocarbonyl)pyridine 1a,b as starting material. Structures of the newly synthesized compounds were established by IR, 1H and 13C-NMR, and MS spectral data and elemental analysis. The in-vitro cytotoxicity activity was investigated for all compounds against MCF-7 and HepG-2 cell lines and the majority of the compounds showed potent anticancer activity against the tested cell lines in comparison with the reference drugs. Out of the macrocyclic pyrido-pentapeptide based compounds, 5c showed encouraging inhibitory activity on MCF-7 and HepG-2 cell lines with IC50 values 9.41 ± 1.25 and 7.53 ± 1.33 μM, respectively. Interestingly, 5c also demonstrated multitarget profile and excellent inhibitory activity towards VEGFR-2, CDK-2 and PDGFRβ kinases. Furthermore, molecular modeling studies of the compound 5c revealed its possible binding modes into the active sites of those kinases. View Full-Text
Keywords: macrocyclic pentapeptides; in vitro anticancer activity; multitarget; molecular modeling studies macrocyclic pentapeptides; in vitro anticancer activity; multitarget; molecular modeling studies
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Amr, A.E.-G.; Abo-Ghalia, M.H.; Moustafa, G.O.; Al-Omar, M.A.; Nossier, E.S.; Elsayed, E.A. Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors. Molecules 2018, 23, 2416.

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