Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins

Mai CW 1 , Yaeghoobi M 2 , Abd-Rahman N 2 , Kang YB 1 , Pichika MR 3

Affiliations 

  • 1 Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
  • 2 Drug Design and Development Research Group, Department of Chemistry, University of Malaya, Kuala Lumpur, Malaysia
  • 3 Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. Electronic address: mallikarjunarao_pichika@imu.edu.my
Eur J Med Chem, 2014 Apr 22;77:378-87.
PMID: 24675137 DOI: 10.1016/j.ejmech.2014.03.002

Abstract

In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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