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Total Synthesis of Piperine and Derivatives: Antimicrobial and Cytotoxic Activities
Jenifer Reine Ngnouzouba Kuete1,2, Vaderament-Alexe Nchiozem-Ngnitedem2, Eric Sperlich2
1Department of Chemistry, Faculty of Science, University of Dschang, Dschang, P.O. Box 67 67, Cameroon.
Abstract:
Piperine is a secondary metabolite derived from plants and fungi and exhibits a wide range of biological properties including antimicrobial, anticancer, anti-inflammatory, and antidiabetic activities. In the present study, the total synthesis of piperine (7a) and related analogues 7b-l was achieved starting from (E)-3,4-(methylenedioxy)-cinnamic acid (5) through PyBOP-mediated coupling with various amines 6. Seven of these analogues (compounds 7d, 7f-j and 7l) are hereby synthesized for the first time. Piperine (7a) displayed antifungal activity against Rhodotorula glutinis DSM-10134 (MIC value of 16.6 μg/mL) while piperic acid (5), piperine (7a), and its analogue 7d were active against the fungus Mucor hiemalis DSM2656 with MICs of 66.6, 33.3, and 33.3 μg/mL, respectively. Furthermore, the analogue 7d exhibited moderate activity against some cancer cell lines with IC50 values ranging from 7 to 21 μg/mL.
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