Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents

Daniel Plano, Deepkamal N. Karelia, Manoj K. Pandey, Julian E. Spallholz, Shantu Amin, Arun K. Sharma

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The synthesis and anticancer evaluation of novel selenium-nonsteroidal anti-inflammatory drug (Se-NSAID) hybrid molecules are reported. The Se-aspirin analogue 8 was identified as the most effective agent in reducing the viability of different cancer cell lines, particularly colorectal cancer (CRC) cells, was more selective toward cancer cells than normal cells, and was >10 times more potent than 5-FU, the current therapy for CRC. Compound 8 inhibits CRC growth via the inhibition of the cell cycle in G1 and G2/M phases and reduces the cell cycle markers like cyclin E1 and B1 in a dose dependent manner; the inhibition of the cell cycle may be dependent on the ability of 8 to induce p21 expression. Furthermore, 8 induces apoptosis by activating caspase 3/7 and PARP cleavage, and its longer exposure causes increase in intracellular ROS levels in CRC cells. Taken together, 8 has the potential to be developed further as a chemotherapeutic agent for CRC.

Original languageEnglish (US)
Pages (from-to)1946-1959
Number of pages14
JournalJournal of Medicinal Chemistry
Volume59
Issue number5
DOIs
StatePublished - Mar 10 2016

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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