Abstract
Abstract A series of novel twenty-eight rigid 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines were synthesized and evaluated for their topoisomerase inhibitory activity as well as their cytotoxicity against several human cancer cell lines. Generally, hydroxylated compounds (16-18, 22-25, and 29-31) containing furyl or thienyl moiety at 4-position of central pyridine exhibited strong topoisomerase I and II inhibitory activity compared to positive control, camptothecin and etoposide, respectively, in low micromolar range. Structure-activity relationship study revealed that indenopyridine compounds with hydroxyl group at 2-phenyl ring in combination with furyl or thienyl moiety at 4-position are important for topoisomerase inhibition. Compounds (22-25) which contain hydroxyl group at meta position of the 2-phenyl ring at 2-position and furanyl or thienyl substitution at 4-position of indenopyridine, showed concrete correlations between topo I and II inhibitory activity, and cytotoxicity against evaluated human cancer cell lines.
Original language | English |
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Article number | 12243 |
Pages (from-to) | 3499-3512 |
Number of pages | 14 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 23 |
Issue number | 13 |
DOIs | |
State | Published - 2015 |
Bibliographical note
Funding Information:This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2012R1A2A2A01046188 , NRF-2012R1A1A4A01015415 , NRF-2007-0056420 and NRF-2013R1A1A2060408 ) and by a grant of the Korean Health Technology R&D Project funded by Ministry of Health & Welfare, Republic of Korea ( HI14C2469 ), and by the 2012 Yeungnam University Research Grant.
Publisher Copyright:
© 2015 Elsevier Ltd.
Keywords
- Anticancer agents
- Cytotoxicity
- Hydroxylated 2-phenyl-4-aryl-5Hindeno[1,2-b]pyridines
- Topoisomerase I and II inhibitor