当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Novel 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridines as potent DNA non-intercalative topoisomerase catalytic inhibitors.

Novel 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridines as potent DNA non-intercalative topoisomerase catalytic inhibitors.

Abstract：

:On the basis of previous reports on the importance of thienyl, furyl or phenol group substitution on 5H-indeno[1,2-b]pyridine skeleton, a new series of rigid 2-aryl-4-(4'-hydroxyphenyl)-5H-indeno[1,2-b]pyridine derivatives were systematically designed and synthesized. Topoisomerase inhibitory activity and antiproliferative activity of all the synthesized compounds were determined using human colorectal (HCT15), breast (T47D), prostate (DU145) and cervix (HeLa) cancer cells. Compounds 9, 10, 12, 13, 15, 16, 18 and 19 with thienyl or furyl moiety at the 2-position and hydroxyl group at the meta or para positions of 4-phenyl ring displayed strong to moderate topoisomerase IIα (topo IIα) inhibitory activity and significant antiproliferative activity. The evaluation of compound 16 to determine its mechanism of action was performed with topo IIα-DNA cleavable complex, topo IIα-mediated ATPase assay, DNA unwinding and in vitro and ex vivo topo IIα relaxation assay. Compound 16 functioned as a DNA non-intercalative topo IIα catalytic inhibitor with better potency than etoposide in T47D breast cancer cells. Molecular docking study revealed that compound 16 cannot intercalate into regularly stacked base-pairs of DNA duplex but can interact or intercalate to topo IIα-bound DNA.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Park S,Kadayat TM,Jun KY,Thapa Magar TB,Bist G,Shrestha A,Lee ES,Kwon Y

doi

10.1016/j.ejmech.2016.09.019

subject

Has Abstract

pub_date

2017-01-05 00:00:00

pages

14-28

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(16)30750-4

journal_volume

125

pub_type

杂志文章

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