Abstract
A series of eighteen trihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of each phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds exhibited strong and selective topoisomerase II inhibitory activity compared to the positive control, etoposide, and also displayed significant cytotoxicity in low micromolar range. Trihydroxylated 2,4,6-triphenyl pyridines were more potent than mono- and di-hydroxylated 2,4,6-triphenyl pyridines, which have been previously studied in our research group. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for the most compounds. Molecular docking study shows qualitatively consistent with the results of biological assays.
Original language | English |
---|---|
Pages (from-to) | 555-565 |
Number of pages | 11 |
Journal | European Journal of Medicinal Chemistry |
Volume | 84 |
DOIs | |
State | Published - 12 Sep 2014 |
Bibliographical note
Funding Information:This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2012R1A2A2A01046188 ).
Keywords
- Anticancer agents
- Cytotoxicity
- Docking study
- Topo II inhibitory activity
- Topoisomerase I
- Topoisomerase II
- Trihydroxylated 2,4,6-triphenyl pyridines