TY - JOUR
T1 - Design, synthesis and evaluation of potential inhibitors for poly(ADP-ribose) polymerase members 1 and 14
AU - Kam, Caleb M
AU - Tauber, Amanda L
AU - Levonis, Stephan M
AU - Schweiker, Stephanie S
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097210158&partnerID=8YFLogxK
U2 - 10.4155/fmc-2020-0218
DO - 10.4155/fmc-2020-0218
M3 - Article
C2 - 33225736
SN - 1756-8927
VL - 12
SP - 2179
EP - 2190
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 24
ER -