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.
Bibliographical noteFunding 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.
© 2015 Elsevier Ltd.
- Anticancer agents
- Hydroxylated 2-phenyl-4-aryl-5Hindeno[1,2-b]pyridines
- Topoisomerase I and II inhibitor