Design, synthesis and evaluation of potential inhibitors for poly(ADP-ribose) polymerase members 1 and 14

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Poly(ADP-ribose) polymerase (PARP) members PARP1 and PARP14 belong to an 18-member superfamily of post-translational modifying enzymes. A library of 9 novel non-NAD analog amine compounds was designed, synthesized and evaluated for inhibitory activity against PARP1 and PARP14. Both in silico studies and in vitro assays identified compound 2 as a potential PARP1 inhibitor, inhibiting activity by 93 ± 2% (PARP14 inhibition: 0 ± 6%), and 7 as a potential PARP14 inhibitor, inhibiting activity by 91 ± 2% (PARP1 inhibition: 18 ± 4%), at 10-μm concentration. Key in silico interactions with TYR907 in PARP1 and TYR1620 and TYR1646 in PARP14 have been identified. Compound 2 and compound 7 have been identified as potential leads for the development of selective PARP inhibitors.

Original languageEnglish
Pages (from-to)2179-2190
Number of pages12
JournalFuture Medicinal Chemistry
Volume12
Issue number24
Early online date23 Nov 2020
DOIs
Publication statusPublished - Dec 2020

Fingerprint

Dive into the research topics of 'Design, synthesis and evaluation of potential inhibitors for poly(ADP-ribose) polymerase members 1 and 14'. Together they form a unique fingerprint.

Cite this