Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

Idris Raji, Fatima Yadudu, Emily Janeira, Shaghayegh Fathi, Lindsey Szymczak, James Richard Kornacki, Kensei Komatsu, Jian Dong Li, Milan Mrksich, Adegboyega K. Oyelere*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


We herein disclose a series of compounds with potent inhibitory activities towards histone deacetylases (HDAC) and cyclooxygenases (COX). These compounds potently inhibited the growth of cancer cell lines consistent with their anti-COX and anti-HDAC activities. While compound 2b showed comparable level of COX-2 selectivity as celecoxib, compound 11b outperformed indomethacin in terms of selectivity towards COX-2 relative to COX-1. An important observation with our lead compounds (2b, 8, 11b, and 17b) is their enhanced cytotoxicity towards androgen dependent prostate cancer cell line (LNCaP) relative to androgen independent prostate cancer cell line (DU-145). Interestingly, compounds 2b and 17b arrested the cell cycle progression of LNCaP in the S-phase, while compound 8 showed a G0/G1 arrest, similar to SAHA. Relative to SAHA, these compounds displayed tumor-selective cytotoxicity as they have low anti-proliferative activity towards healthy cells (VERO); an attribute that makes them attractive candidates for drug development.

Original languageEnglish (US)
Pages (from-to)1202-1218
Number of pages17
JournalBioorganic and Medicinal Chemistry
Issue number3
StatePublished - 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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