2. Academic Validation
  3. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity

Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity

  • Eur J Med Chem. 2014 Jun 23:81:192-203. doi: 10.1016/j.ejmech.2014.05.019.
Ratchanok Pingaew 1,  Prasit Mandi 2,  Chanin Nantasenamat 2,  Supaluk Prachayasittikul 3,  Somsak Ruchirawat 4,  Virapong Prachayasittikul 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand. Electronic address: ratchanok@swu.ac.th.
  • 2 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand; Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 3 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
  • 4 Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand; Program in Chemical Biology, Chulabhorn Graduate Institute, Bangkok 10210, Thailand; Center of Excellence on Environmental Health and Toxicology, Commission on Higher, Education (CHE), Ministry of Education, Thailand.
  • 5 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
PMID: 24836071 DOI: 10.1016/j.ejmech.2014.05.019
Abstract

A novel series of N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinolines (14-33) containing triazole moiety were designed and synthesized through rational cycloadditions using the modified Pictet-Spengler reaction and the Click Chemistry. Antiproliferative activity against four Cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) revealed that many substituted triazole analogs of benzoates (20, 29) and benzaldehydes (30, 32) exhibited Anticancer activity against all of the tested Cancer cell lines in which the ester analog 20 was shown to be the most potent compound against HuCCA-1 (IC50 = 0.63 μM) and A549 (IC50 = 0.57 μM) cell lines. Triazoles bearing phenyl (15, 24), tolyl (26, 27), acetophenone (19), benzoate (20, 29), benzaldehyde (21, 30) and naphthalenyl (25) substituents showed stronger Anticancer activity against HepG2 cells than that of the etoposide. Interestingly, the p-tolyl analog (27) displayed the most potent inhibitory activity (IC50 = 0.56 μM) against HepG2 cells without affecting normal cells. Of the investigated tetrahydroisoquinoline-triazoles, the promising compounds 20 and 27 were selected for molecular docking against AKR1C3, which was identified to be a plausible target site.

Keywords

AKR1C3; Antiproliferative activity; Isoquinoline; Molecular docking; Pictet–Spengler reaction; Triazole.

Figures