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Synthesis of some tropane-based compounds targeting colon cancer

Background: In continuation of a previous work concerned with the anticancer activity of some 8-alkyl-2,4-bisarylidene-8-nortropan-3-ones, this work focuses on further modification to the tropane/pyran fused skeleton aiming to obtain improved anticancer activity. Methodology: Reaction of 8-alkyl-2,4...

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Main Authors: Samir, Nermin (Author) , George, Riham F (Author) , Elrazaz, Eman Z (Author) , Ayoub, Iriny M (Author) , Shalaby, ElSayed M (Author) , Plaisier, Jasper R (Author) , Demitri, Nicola (Author) , Wink, Michael (Author)
Format: Article (Journal)
Language:English
Published: 23 November 2020
In: Future medicinal chemistry
Year: 2020, Volume: 12, Issue: 23, Pages: 2123-2140
ISSN:1756-8927
DOI:10.4155/fmc-2020-0097
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4155/fmc-2020-0097
Verlag, lizenzpflichtig, Volltext: https://www.future-science.com/doi/10.4155/fmc-2020-0097
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Author Notes:Nermin Samir, Riham F George, Eman Z Elrazaz, Iriny M Ayoub, ElSayed M Shalaby, Jasper R Plaisier, Nicola Demitri and Michael Wink
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Summary:Background: In continuation of a previous work concerned with the anticancer activity of some 8-alkyl-2,4-bisarylidene-8-nortropan-3-ones, this work focuses on further modification to the tropane/pyran fused skeleton aiming to obtain improved anticancer activity. Methodology: Reaction of 8-alkyl-2,4-bisarylidene-8-nortropan-3-ones 1-21 with malononitrile under basic conditions afforded tropane/pyran hybrids 22-40 and tropane/pyridine hybrids 41, 42. X-ray crystallography for compounds 22 and 41 as representative examples confirmed their structures. They were tested for their anticancer activity in the HCT116 cell line. Results: Compounds 26 and 33 were the most active compounds with IC50 values of 3.39 and 0.01 μM against HCT116. Moreover, they revealed cyclin-dependent kinase-2 (CDK2) inhibition with IC50 = 104.91 and 49.13 nM, respectively. Furthermore, molecular docking of compounds 26 and 33 in the active site of CDK2 confirmed the obtained results. Conclusion: Tropane/pyran scaffold can be considered as a promising core for anticancer agents acting as CDK2 inhibitors.
Item Description:Gesehen am 03.02.2021
Physical Description:Online Resource
ISSN:1756-8927
DOI:10.4155/fmc-2020-0097

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