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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5498-5511
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number11
DOIs
StatePublished - Nov 1 2011

Keywords

  • Cell adhesion molecules
  • Cinnamates
  • Endothelial cells
  • Thiocinnamates thionocinnamates

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Kumar, S., Singh, B. K., Arya, P., Malhotra, S., Thimmulappa, R., Prasad, A. K., Van Der Eycken, E., Olsen, C. E., Depass, A. L., Biswal, S., Parmar, V. S., & Ghosh, B. (2011). Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells. European Journal of Medicinal Chemistry, 46(11), 5498-5511. https://doi.org/10.1016/j.ejmech.2011.09.008