European Journal of Medicinal Chemistry 2011-11-01

Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells.

Sarvesh Kumar, Brajendra K Singh, Pragya Arya, Shashwat Malhotra, Rajesh Thimmulappa, Ashok K Prasad, Erik Van der Eycken, Carl E Olsen, Anthony L DePass, Shyam Biswal, Virinder S Parmar, Balaram Ghosh

Index: Eur. J. Med. Chem. 46 , 5498-511, (2011)

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Abstract

In the present study, we report the design and synthesis of novel analogs of cinnamates, thiocinnamates and thionocinnamates and evaluated the potencies of these analogs to inhibit TNF-α induced ICAM-1 expression on human endothelial cells. By using whole cell-ELISA, our screening data demonstrated that ethyl 3',4',5'-trimethoxythionocinnamate (ETMTC) is the most potent inhibitor of TNF-α induced ICAM-1, VCAM-1 and E-selectin. As functional consequences, ETMTC abrogated TNF-α induced adhesion of neutrophils to the endothelial monolayer. Structure-activity relationship studies revealed the critical role of the chain-length of the alkyl group in the alcohol moiety, number of methoxy groups in the aromatic ring of the cinnamoyl moiety and the presence of the α, β- C-C double bond in the thiocinnamates and thionocinnamates.Copyright © 2011 Elsevier Masson SAS. All rights reserved.