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Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
Bioorg Med Chem. 2016 10 01; 24(19):4731-4740.BM

Abstract

8,9-Dihydro-2,4,7,9a-tetraazabenzo[cd]azulen-6(7H)-ones were designed and synthesized as a new class of PARP-1/2 inhibitors. The compounds displayed a variable pattern of PARP-1/2 enzymes inhibition profile that, in part, paralleled the antiproliferative activity in cell lines. Among them, compound 9e exhibited not only the significant IC50 value of 28nM in the PARP-1 and 7.7nM in PARP-2 enzyme assay, but also a profound synergic efficacy combined with temozolomide with PF50 values of 2.6, 2.5, and 6.5 against MDA-MB-468, SW-620 and A549 and cell line, respectively.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Li H
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Hu Y
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
Wang X
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
He G
Hefei YiGong Pharmaceutical Co. Ltd, Hefei 230088, China.
Xu Y
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
Zhu Q
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.

MeSH

Antineoplastic AgentsAzulenesCell Line, TumorCell ProliferationDrug DesignHumansModels, MolecularNeoplasmsPoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) Polymerases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27561983

Citation

Li, Hui, et al. "Novel Tricyclic Poly (ADP-ribose) Polymerase-1/2 Inhibitors With Potent Anticancer Chemopotentiating Activity: Design, Synthesis and Biological Evaluation." Bioorganic & Medicinal Chemistry, vol. 24, no. 19, 2016, pp. 4731-4740.
Li H, Hu Y, Wang X, et al. Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation. Bioorg Med Chem. 2016;24(19):4731-4740.
Li, H., Hu, Y., Wang, X., He, G., Xu, Y., & Zhu, Q. (2016). Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation. Bioorganic & Medicinal Chemistry, 24(19), 4731-4740. https://doi.org/10.1016/j.bmc.2016.08.016
Li H, et al. Novel Tricyclic Poly (ADP-ribose) Polymerase-1/2 Inhibitors With Potent Anticancer Chemopotentiating Activity: Design, Synthesis and Biological Evaluation. Bioorg Med Chem. 2016 10 1;24(19):4731-4740. PubMed PMID: 27561983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation. AU - Li,Hui, AU - Hu,Yan, AU - Wang,Xueyan, AU - He,Guangwei, AU - Xu,Yungen, AU - Zhu,Qihua, Y1 - 2016/08/11/ PY - 2016/06/18/received PY - 2016/08/10/revised PY - 2016/08/11/accepted PY - 2016/8/27/entrez PY - 2016/8/27/pubmed PY - 2017/7/14/medline KW - Anticancer KW - Inhibitors KW - PARP-1/2 KW - Tricyclic SP - 4731 EP - 4740 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 24 IS - 19 N2 - 8,9-Dihydro-2,4,7,9a-tetraazabenzo[cd]azulen-6(7H)-ones were designed and synthesized as a new class of PARP-1/2 inhibitors. The compounds displayed a variable pattern of PARP-1/2 enzymes inhibition profile that, in part, paralleled the antiproliferative activity in cell lines. Among them, compound 9e exhibited not only the significant IC50 value of 28nM in the PARP-1 and 7.7nM in PARP-2 enzyme assay, but also a profound synergic efficacy combined with temozolomide with PF50 values of 2.6, 2.5, and 6.5 against MDA-MB-468, SW-620 and A549 and cell line, respectively. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/27561983/Novel_tricyclic_poly__ADP_ribose__polymerase_1/2_inhibitors_with_potent_anticancer_chemopotentiating_activity:_Design_synthesis_and_biological_evaluation_ DB - PRIME DP - Unbound Medicine ER -