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Planta Med 2015; 81(12/13): 1065-1074
DOI: 10.1055/s-0035-1546165
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Piperine Congeners as Inhibitors of Vascular Smooth Muscle Cell Proliferation[*]

Christina E. Mair   #
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
2   Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innsbruck, Austria
,
Rongxia Liu   #
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
4   School of Pharmacy, Yantai University, Yantai, China
,
Atanas G. Atanasov
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Laurin Wimmer
3   Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
,
Daniel Nemetz-Fiedler
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Nadine Sider
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Elke H. Heiss
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Marko D. Mihovilovic
3   Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
,
Verena M. Dirsch
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
,
Judith M. Rollinger
1   Department of Pharmacognosy, University of Vienna, Vienna, Austria
2   Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innsbruck, Austria
› Author Affiliations
Further Information

Publication History

received 12 March 2015
revised 01 May 2015

accepted 05 May 2015

Publication Date:
01 July 2015 (online)

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Abstract

Successful vascular healing after percutaneous coronary interventions is related to the inhibition of abnormal vascular smooth muscle cell proliferation and efficient re-endothelialization. In the search for vascular smooth muscle cell anti-proliferative agents from natural sources we identified piperine (1), the main pungent constituent of the fruits from Piper nigrum (black pepper). Piperine inhibited vascular smooth muscle cell proliferation with an IC50 of 21.6 µM, as quantified by a resazurin conversion assay. Investigations of ten piperamides isolated from black pepper fruits and 15 synthesized piperine derivatives resulted in the identification of three potent vascular smooth muscle cell proliferation inhibitors: the natural alkaloid pipertipine (4), and the two synthetic derivatives (2E,4E)-N,N-dibutyl-5-(3,5-dimethoxyphenyl)penta-2,4-dienamide (14) and (E)-N,N-dibutyl-3-(naphtho[2,3-d][1,3]dioxol-5-yl)acrylamide (20). They showed IC50 values of 3.38, 6.00, and 7.85 µM, respectively. Furthermore, the synthetic compound (2E,4E)-5-(4-fluorophenyl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (12) was found to be cell type selective, by inhibiting vascular smooth muscle cell proliferation with an IC50 of 11.8 µM without influencing the growth of human endothelial cells.

Key words

Piper nigrum - Piperaceae - Piperine - vascular smooth muscle cells - inhibition of VSMC proliferation - SAR - restenosis

* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.


# These authors contributed equally to this work.


 

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