View : 19 Download: 0
Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents
- Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents
- Thapa, Pritam; Jun, Kyu-Yeon; Kadayat, Tara Man; Park, Chanmi; Zheng, Zhi; Magar, Til Bahadur Thapa; Bist, Ganesh; Shrestha, Aarajana; Na, Younghwa; Kwon, Youngjoo; Lee, Eung-Seok
- Ewha Authors
- 권영주; 전규연
- SCOPUS Author ID
- Issue Date
- Journal Title
- BIOORGANIC & MEDICINAL CHEMISTRY
- 0968-0896; 1464-3391
- vol. 23, no. 19, pp. 6454 - 6466
- Antiproliferative agents; Cytotoxicity; Hydroxylated 4-phenyl-2-aryl chromenopyridines; Structure-activity relationships; Topoisomerase II inhibitor
- PERGAMON-ELSEVIER SCIENCE LTD
- SCI; SCIE; SCOPUS
- To develop novel selective topoisomerase II inhibitors, we designed and synthesized a series of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines and evaluated their topoisomerase inhibitory activity and cytotoxicity against three human cancer cell lines (DU145, HCT15, and T47D) and a normal cell line (MCF10A). All of the prepared compounds displayed stronger or similar topoisomerase II inhibitory activity as well as cytotoxicity against three human cancer cell lines compared to etoposide. Compounds 10a, 10g, 11a, 11f, 11g, 12a, 12f, and 12g especially showed stronger topoisomerase II inhibitory activity as compared to etoposide at both 100 mu M and 20 mu M. A structure-activity relationship study revealed that hydroxyphenyl moiety at 4-position of pyridine and ortho-hydroxyphenyl or thienyl moiety at 2-position of pyridine has an important role in displaying selective topoisomerase II inhibition. The compound 12b with para-hydroxyphenyl and meta-hydroxyphenyl at 4- and 2-position of pyridine, respectively, showed the most significant cytotoxicity against all three cancer cell lines, whereas less cytotoxicity to a normal cell line as compared to adriamycin. (C) 2015 Elsevier Ltd. All rights reserved.
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.