Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors

Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors Poly (ADP-ribose) polymerase (PARP-1) is a well-established nuclear protein with prominent role in signaling and DNA repair. Various clinical candidates have been identified with the role in PARP-1 inhibition. Based on the pharmacophoric features identified from previous studies and molecular docking interactions, thiazolidine-2,4-dione derivatives have been evaluated for their PARP inhibitory activity. From an in vitro assay, 5-((1-(4-isopropylbenzyl)-1H-indol-3-yl)methylene)thiazolidine-2,4-dione (16) was identified as a potent inhibitor having low micromolar inhibitory activity $$(\hbox {IC}_{50} \,{=}\, 0.74 \,\pm \, 0.25\,\upmu \hbox {M})$$ ( IC 50 = 0.74 ± 0.25 μ M ) . Thus, a structure-based design approach utilized in the present study helped to identify thiazolidine-2,4-dione as a novel scaffold against PARP-1 for potential development of potent anticancer therapeutics. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Diversity Springer Journals

Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors

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Publisher
Springer International Publishing
Copyright
Copyright © 2017 by Springer International Publishing Switzerland
Subject
Life Sciences; Biochemistry, general; Organic Chemistry; Polymer Sciences; Pharmacy
ISSN
1381-1991
eISSN
1573-501X
D.O.I.
10.1007/s11030-017-9754-7
Publisher site
See Article on Publisher Site

Abstract

Poly (ADP-ribose) polymerase (PARP-1) is a well-established nuclear protein with prominent role in signaling and DNA repair. Various clinical candidates have been identified with the role in PARP-1 inhibition. Based on the pharmacophoric features identified from previous studies and molecular docking interactions, thiazolidine-2,4-dione derivatives have been evaluated for their PARP inhibitory activity. From an in vitro assay, 5-((1-(4-isopropylbenzyl)-1H-indol-3-yl)methylene)thiazolidine-2,4-dione (16) was identified as a potent inhibitor having low micromolar inhibitory activity $$(\hbox {IC}_{50} \,{=}\, 0.74 \,\pm \, 0.25\,\upmu \hbox {M})$$ ( IC 50 = 0.74 ± 0.25 μ M ) . Thus, a structure-based design approach utilized in the present study helped to identify thiazolidine-2,4-dione as a novel scaffold against PARP-1 for potential development of potent anticancer therapeutics.

Journal

Molecular DiversitySpringer Journals

Published: Jun 26, 2017

References

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