TY - JOUR
T1 - Design, synthesis and biological evaluation of 1,3-diphenylbenzo[f][1,7]naphthyrdines
AU - Arepalli, Sateesh Kumar
AU - Park, Byeongwoo
AU - Lee, Kiho
AU - Jo, Hyunji
AU - Jun, Kyu Yeon
AU - Kwon, Youngjoo
AU - Kang, Jong Soon
AU - Jung, Jae Kyung
AU - Lee, Heesoon
N1 - Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF- 2015R1D1A1A01058142 ), Korea Research Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2016H1D3A1937140 ) and Medical Research Center Program ( 2017R1A5A2015541 ).
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017
Y1 - 2017
N2 - A novel series of twenty 1,3-diphenylbenzo[f][1,7]benzonaphthyrdine derivatives were designed and synthesized through intermolecular imino Diels-Alder reaction. Their in vitro cytotoxic activities were evaluated against six human cancer cell lines (NCIH23, HCT15, NUGC-3, ACHN, PC-3, and MDA-MB-231). Majority of synthesized compounds exhibited significant cytotoxic activities against all tested human cancer cell lines. Among them 4l, 4m, and 4o derivatives exhibited most promising cytotoxic activities. Furthermore these compounds were evaluated against human Topoisomerase IIα inhibition. Interestingly, the compound 4l exhibited 1.3 and 1.2 times more potent human Topoisomerase IIα inhibition than the reference drug etoposide in both 100 µM and 20 µM concentrations respectively. Molecular docking studies for the compound 4l have also been executed by Sybyl X-2.1 in which it reveals the binding site of the compound 4l with topo IIα DNA cleavage site where etoposide was situated. The benzo[f][1,7]naphthyridine ring was stacked between the DNA bases of the cleavage site.
AB - A novel series of twenty 1,3-diphenylbenzo[f][1,7]benzonaphthyrdine derivatives were designed and synthesized through intermolecular imino Diels-Alder reaction. Their in vitro cytotoxic activities were evaluated against six human cancer cell lines (NCIH23, HCT15, NUGC-3, ACHN, PC-3, and MDA-MB-231). Majority of synthesized compounds exhibited significant cytotoxic activities against all tested human cancer cell lines. Among them 4l, 4m, and 4o derivatives exhibited most promising cytotoxic activities. Furthermore these compounds were evaluated against human Topoisomerase IIα inhibition. Interestingly, the compound 4l exhibited 1.3 and 1.2 times more potent human Topoisomerase IIα inhibition than the reference drug etoposide in both 100 µM and 20 µM concentrations respectively. Molecular docking studies for the compound 4l have also been executed by Sybyl X-2.1 in which it reveals the binding site of the compound 4l with topo IIα DNA cleavage site where etoposide was situated. The benzo[f][1,7]naphthyridine ring was stacked between the DNA bases of the cleavage site.
KW - 1,3-Diphenylbenzo[f][1,7]benzonaphthyrdines
KW - Cytotoxic agents
KW - Human Topoisomerase IIα inhibitors
KW - Imino Diels-Alder reaction
KW - Molecular docking studies
UR - http://www.scopus.com/inward/record.url?scp=85028600868&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2017.08.030
DO - 10.1016/j.bmc.2017.08.030
M3 - Article
C2 - 28870801
AN - SCOPUS:85028600868
SN - 0968-0896
VL - 25
SP - 5586
EP - 5597
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 20
ER -