Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines

Tara Man Kadayat; Chanju Song; Somin Shin; Til Bahadur Thapa Magar; Ganesh Bist; Aarajana Shrestha; Pritam Thapa; Younghwa Na; Youngjoo Kwon; Eung Seok Lee

doi:10.1016/j.bmc.2015.04.031

Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines

Tara Man Kadayat, Chanju Song, Somin Shin, Til Bahadur Thapa Magar, Ganesh Bist, Aarajana Shrestha, Pritam Thapa, Younghwa Na, Youngjoo Kwon, Eung Seok Lee

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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
Article number	12243
Pages (from-to)	3499-3512
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	23
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2015.04.031
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

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10.1016/j.bmc.2015.04.031

Cite this

Kadayat, T. M., Song, C., Shin, S., Magar, T. B. T., Bist, G., Shrestha, A., Thapa, P., Na, Y., Kwon, Y., & Lee, E. S. (2015). Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines. Bioorganic and Medicinal Chemistry, 23(13), 3499-3512. Article 12243. https://doi.org/10.1016/j.bmc.2015.04.031

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title = "Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines",

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.",

keywords = "Anticancer agents, Cytotoxicity, Hydroxylated 2-phenyl-4-aryl-5Hindeno[1,2-b]pyridines, Topoisomerase I and II inhibitor",

author = "Kadayat, {Tara Man} and Chanju Song and Somin Shin and Magar, {Til Bahadur Thapa} and Ganesh Bist and Aarajana Shrestha and Pritam Thapa and Younghwa Na and Youngjoo Kwon and Lee, {Eung Seok}",

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: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

doi = "10.1016/j.bmc.2015.04.031",

language = "English",

volume = "23",

pages = "3499--3512",

journal = "Bioorganic and Medicinal Chemistry",

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Kadayat, TM, Song, C, Shin, S, Magar, TBT, Bist, G, Shrestha, A, Thapa, P, Na, Y, Kwon, Y & Lee, ES 2015, 'Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines', Bioorganic and Medicinal Chemistry, vol. 23, no. 13, 12243, pp. 3499-3512. https://doi.org/10.1016/j.bmc.2015.04.031

Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines. / Kadayat, Tara Man; Song, Chanju; Shin, Somin et al.
In: Bioorganic and Medicinal Chemistry, Vol. 23, No. 13, 12243, 2015, p. 3499-3512.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines

AU - Kadayat, Tara Man

AU - Song, Chanju

AU - Shin, Somin

AU - Magar, Til Bahadur Thapa

AU - Bist, Ganesh

AU - Shrestha, Aarajana

AU - Thapa, Pritam

AU - Na, Younghwa

AU - Kwon, Youngjoo

AU - Lee, Eung Seok

N1 - 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.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Anticancer agents

KW - Cytotoxicity

KW - Hydroxylated 2-phenyl-4-aryl-5Hindeno[1,2-b]pyridines

KW - Topoisomerase I and II inhibitor

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DO - 10.1016/j.bmc.2015.04.031

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SN - 0968-0896

VL - 23

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EP - 3512

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

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ER -

Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of 2-phenyl- or hydroxylated 2-phenyl-4-aryl-5H-indeno[1,2-b]pyridines

Abstract

Bibliographical note

Keywords

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