Synthetic PARP-1 Inhibitors Reported During the Last Decade

Maneesh      Guleria; Pradeep      Kumar; Suresh      Thareja

doi:10.2174/1570180819666220615090709

Abstract

Background: Cancer is the world's second-largest cause of death, and is responsible for an estimated 9.6 million mortality cases in 2018. Poly-ADP-ribose polymerases (PARPs) are enzymes and a family of proteins involved in many cellular processes, including DNA repair, gene regulation, chromatin remodeling, and apoptosis. The first characterized and best-known member of the PARP family is poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 is a major protein for DNA single-strand breaks in the BER pathway (base excision repair) (SSBs).

Objective: The objective of this article was to compile synthetic PARP-1 inhibitors reported in the last decade.

Methods: In the present manuscript, bibliographic investigation was carried out by scrutinizing peerreviewed articles from online/offline databases. The inclusion criteria consisted of the most relevant studies indicating the relationship between PARP-1 and cancer in textbooks/edited books and peer-reviewed papers from scientific databases, like SCOPUS, PUBMED, NISCAIR, and Google Scholar since 2010 to 2020. Only the studies published in English language were searched/considered. The exclusion criteria consisted of the studies on other PARP isoforms than PARP-1. The studies thus obtained were classified according to the heterocyclic moieties, year of publication, etc. The data compiled in this article is a systematic review of the reported studies.

Results: The literature reports indicated that a number of PARP-1 inhibitors reported have IC50 value in nanomolar concentration.

Conclusion: PARP-1 is an essential target for anti-cancer drug discovery. Further research on more effective and safe PARP-1 inhibitors needs to be carried out, and we may discover some novel PARP-1 inhibitors in the near future.

Keywords: Cancer, PARP, PARP-1, FDA-approved inhibitors, PARP-1 inhibitors, SSBs.

[1]
Oh, C.M.; Lee, D.; Kong, H.J.; Lee, S.; Won, Y.J.; Jung, K.W.; Cho, H. Causes of death among cancer patients in the era of cancer survivorship in Korea: Attention to the suicide and cardiovascular mortality. Cancer Med.,  2020, 9(5), 1741-1752.
 [http://dx.doi.org/10.1002/cam4.2813] [PMID:  31960609]

[2]
Mansoorinasab, M.; Abdolhoseinpour, H. A review and update of vertebral fractures due to metastatic tumors of various sites to the spine: Percutaneous vertebroplasty. Interv. Med. Appl. Sci.,  2018, 10(1), 1-6.
 [http://dx.doi.org/10.1556/1646.10.2018.03] [PMID:  30363329]

[3]
Hassanpour, S.H.; Dehghani, M. Review of cancer from perspective of molecular. J. Cancer Res. Pract.,  2017, 4(4), 127-129.
 [http://dx.doi.org/10.1016/j.jcrpr.2017.07.001]

[4]
WHO. Cancer 12. Cancer,  2018, 2018

[5]
Cancer, B.O.F. WHO Cancer Report; Global Profile, 2020. 

[6]
Ray Chaudhuri, A.; Nussenzweig, A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat. Rev. Mol. Cell Biol.,  2017, 18(10), 610-621.
 [http://dx.doi.org/10.1038/nrm.2017.53] [PMID:  28676700]

[7]
Jubin, T.; Kadam, A.; Jariwala, M.; Bhatt, S.; Sutariya, S.; Gani, A.R.; Gautam, S.; Begum, R. The PARP family: Insights into functional aspects of poly (ADP-ribose) polymerase-1 in cell growth and survival. Cell Prolif.,  2016, 49(4), 421-437.
 [http://dx.doi.org/10.1111/cpr.12268] [PMID:  27329285]

[8]
Guo, C.; Wang, L.; Li, X.; Wang, S.; Yu, X.; Xu, K.; Zhao, Y.; Luo, J.; Li, X.; Jiang, B.; Shi, D. Discovery of novel bromophenol-thiosemicarbazone hybrids as potent selective inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) for use in cancer. J. Med. Chem.,  2019, 62(6), 3051-3067.
 [http://dx.doi.org/10.1021/acs.jmedchem.8b01946] [PMID:  30844273]

[9]
Fuertes, A.; Castilla, J.; Alonso, C.; Quevedo, C. Poly (ADP-Ribose) chemotherapy inhibitors in cancer. Anticancer Drugs,  2006, 39-53.
 [PMID:  18221025]

[10]
Chen, A. PARP inhibitors: Its role in treatment of cancer. Chin. J. Cancer,  2011, 30(7), 463-471.
 [http://dx.doi.org/10.5732/cjc.011.10111] [PMID:  21718592]

[11]
Slade, D. PARP and PARG inhibitors in cancer treatment. NLM,  2020, 34(5-6), 360-394.
 [http://dx.doi.org/10.1101/gad.334516.119] [PMID:  32029455]

[12]
Wang, L.; Liang, C.; Li, F.; Guan, D.; Wu, X.; Fu, X.; Lu, A.; Zhang, G. PARP1 in Carcinomas and PARP1 Inhibitors as Antineoplastic Drugs. Int. J. Mol. Sci.,  2017, 18(10), 2111.
 [http://dx.doi.org/10.3390/ijms18102111] [PMID:  28991194]

[13]
Morales, J.; Li, L.; Fattah, F.J.; Dong, Y.; Bey, E.A.; Patel, M.; Gao, J.; Boothman, D.A. Review of poly (ADP-ribose) polymerase (PARP) mechanisms of action and rationale for targeting in cancer and other diseases. Crit. Rev. Eukaryot. Gene Expr.,  2014, 24(1), 15-28.
 [http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2013006875] [PMID:  24579667]

[14]
Jones, P.; Altamura, S.; Boueres, J.; Ferrigno, F.; Fonsi, M.; Giomini, C.; Lamartina, S.; Monteagudo, E.; Ontoria, J.M.; Orsale, M.V.; Palumbi, M.C.; Pesci, S.; Roscilli, G.; Scarpelli, R.; Schultz-Fademrecht, C.; Toniatti, C.; Rowley, M. Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J. Med. Chem.,  2009, 52, 7170-7185.
 [http://dx.doi.org/10.1021/jm901188v] [PMID:  19873981]

[15]
Kim, G.; Ison, G.; McKee, A.E.; Zhang, H.; Tang, S.; Gwise, T.; Sridhara, R.; Lee, E.; Tzou, A.; Philip, R.; Chiu, H.J.; Ricks, T.K.; Palmby, T.; Russell, A.M.; Ladouceur, G.; Pfuma, E.; Li, H.; Zhao, L.; Liu, Q.; Venugopal, R.; Ibrahim, A.; Pazdur, R. FDA approval summary: Olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy. Clin. Cancer Res.,  2015, 21(19), 4257-4261.
 [http://dx.doi.org/10.1158/1078-0432.CCR-15-0887] [PMID:  26187614]

[16]
Shen, Y.; Rehman, F.L.; Feng, Y.; Boshuizen, J.; Bajrami, I.; Elliott, R.; Wang, B.; Lord, C.J.; Post, L.E.; Ashworth, A. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin. Cancer Res.,  2013, 19(18), 5003-5015.
 [http://dx.doi.org/10.1158/1078-0432.CCR-13-1391] [PMID:  23881923]

[17]
Results, S; Available, N.R.; Tyne, N.U. Clinical Trials.gov,  2020, 1-3.

[18]
Ye, N.; Chen, C.; Chen, T.T.; Song, Z.; He, J.; Huan, X. Design, Synthesis and Biological Evaluation of a Series of Longer Chain Appendage as Novel PARP1 Inhibitors. J. Med. Chem.,  2013, 56, 2885-2903.
 [http://dx.doi.org/10.1021/jm301825t] [PMID:  23473053]

[19]
Chen, W.H.; Song, S.S.; Qi, M.H.; Huan, X.J.; Wang, Y.Q.; Jiang, H.; Ding, J.; Ren, G.B.; Miao, Z.H.; Li, J. Discovery of potent 2,4-difluoro-linker poly(ADP-ribose) polymerase 1 inhibitors with enhanced water solubility and in vivo anticancer efficacy. Acta Pharmacol. Sin.,  2017, 38(11), 1521-1532.
 [http://dx.doi.org/10.1038/aps.2017.104] [PMID:  28770827]

[20]
Zmuda, F.; Malviya, G.; Blair, A.; Boyd, M.; Chalmers, A.J.; Sutherland, A.; Pimlott, S.L. Synthesis and evaluation of a radioiodinated tracer with specificity for poly (ADP-ribose) polymerase-1 (PARP-1) in vivo. J. Med. Chem.,  2015, 58(21), 8683-8693.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b01324] [PMID:  26469301]

[21]
Tian, Y.; Xie, Z.; Liao, C. Design, synthesis and anticancer activities of novel dual poly(ADP-ribose) polymerase-1/histone deacetylase-1 inhibitors. Bioorg. Med. Chem. Lett.,  2020, 30(8), 127036.
 [http://dx.doi.org/10.1016/j.bmcl.2020.127036] [PMID:  32088129]

[22]
Xin, M.; Sun, J.; Huang, W.; Tang, F.; Liu, Z.; Jin, Q.; Wang, J. Design and synthesis of novel phthalazinone derivatives as potent poly(ADP-ribose)polymerase 1 inhibitors. Future Med. Chem.,  2020, 12(19), 1691-1707.
 [http://dx.doi.org/10.4155/fmc-2020-0009] [PMID:  33012191]

[23]
Wang, L.X.; Zhou, X.B.; Xiao, M.L.; Jiang, N.; Liu, F.; Zhou, W.X.; Wang, X.K.; Zheng, Z.B.; Li, S. Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Bioorg. Med. Chem. Lett.,  2014, 24(16), 3739-3743.
 [http://dx.doi.org/10.1016/j.bmcl.2014.07.001] [PMID:  25086680]

[24]
Elmasry, G.F.; Aly, E.E.; Awadallah, F.M.; El-Moghazy, S.M. Design and synthesis of novel PARP-1 inhibitors based on pyridopyridazinone scaffold. Bioorg. Chem.,  2019, 87, 655-666.
 [http://dx.doi.org/10.1016/j.bioorg.2019.03.068] [PMID:  30952061]

[25]
Almahli, H.; Hadchity, E.; Jaballah, M.Y.; Daher, R.; Ghabbour, H.A.; Kabil, M.M.; Al-Shakliah, N.S.; Eldehna, W.M. Development of novel synthesized phthalazinone-based PARP-1 inhibitors with apoptosis inducing mechanism in lung cancer. Bioorg. Chem.,  2018, 77, 443-456.
 [http://dx.doi.org/10.1016/j.bioorg.2018.01.034] [PMID:  29453076]

[26]
Zhou, J.; Ji, M.; Zhu, Z.; Cao, R.; Chen, X.; Xu, B.; Chen, X.; Xu, B. Discovery of 2-substituted 1H-benzo[d]immidazole-4-carboxamide derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors with in vivo anti-tumor activity. Eur. J. Med. Chem.,  2017, 132, 26-41.
 [http://dx.doi.org/10.1016/j.ejmech.2017.03.013] [PMID:  28340412]

[27]
Abdullah, I.; Chee, C.F.; Lee, Y.K.; Thunuguntla, S.S.R.; Satish Reddy, K.; Nellore, K.; Antony, T.; Verma, J.; Mun, K.W.; Othman, S.; Subramanya, H.; Rahman, N.A. Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH. Bioorg. Med. Chem.,  2015, 23(15), 4669-4680.
 [http://dx.doi.org/10.1016/j.bmc.2015.05.051] [PMID:  26088338]

[28]
Chen, X.; Huan, X.; Liu, Q.; Wang, Y.; He, Q.; Tan, C.; Chen, Y.; Ding, J.; Xu, Y.; Miao, Z.; Yang, C. Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors. Eur. J. Med. Chem.,  2018, 145, 389-403.
 [http://dx.doi.org/10.1016/j.ejmech.2018.01.018] [PMID:  29335205]

[29]
Zhong, Y.; Meng, Y.; Xu, X.; Zhao, L.; Li, Z.; You, Q.; Bian, J. Design, synthesis and evaluation of phthalazinone thiohydantoin-based derivative as potent PARP-1 inhibitors. Bioorg. Chem.,  2019, 91, 103181.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103181] [PMID:  31404795]

[30]
Gangula, M.R.; Kanthaiah, C.; Arts, M.; Vijayakumar, B.; Kanthaiah, C.; Arts, M. Design and Synthesis of 2-substituted-1H- benzimidazole-4- carboxamides as inhibitors of poly (ADP-ribose) polymerase-1. World J. Pharm. Pharm. Sci.,  2014, 1, 2278-4357.

[31]
Yuan, Z.; Chen, S.; Chen, C.; Chen, J.; Chen, C.; Dai, Q.; Gao, C.; Jiang, Y. Design, synthesis and biological evaluation of 4-amidobenzimidazole acridine derivatives as dual PARP and Topo inhibitors for cancer therapy. Eur. J. Med. Chem.,  2017, 138, 1135-1146.
 [http://dx.doi.org/10.1016/j.ejmech.2017.07.050] [PMID:  28763648]

[32]
Wang, J.; Wang, X.; Li, H.; Ji, D.; Li, Y.; Xu, Y.; Zhu, Q. Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors. Bioorg. Med. Chem. Lett.,  2016, 26(16), 4127-4132.
 [http://dx.doi.org/10.1016/j.bmcl.2016.06.045] [PMID:  27353531]

[33]
Zhao, H.; Ji, M.; Cui, G.; Zhou, J.; Lai, F.; Chen, X.; Xu, B. Discovery of novel quinazoline-2,4(1H,3H)-dione derivatives as potent PARP-2 selective inhibitors. Bioorg. Med. Chem.,  2017, 25(15), 4045-4054.
 [http://dx.doi.org/10.1016/j.bmc.2017.05.052] [PMID:  28622906]

[34]
Zhou, J.; Ji, M.; Yao, H.; Cao, R.; Zhao, H.; Wang, X.; Chen, X.; Xu, B. Discovery of quinazoline-2,4(1H,3H)-dione derivatives as novel PARP-1/2 inhibitors: Design, synthesis and their antitumor activity. Org. Biomol. Chem.,  2018, 16(17), 3189-3202.
 [http://dx.doi.org/10.1039/C8OB00286J] [PMID:  29648554]

[35]
Yao, H.; Ji, M.; Zhu, Z.; Zhou, J.; Cao, R.; Chen, X.; Xu, B. Discovery of 1-substituted benzyl-quinazoline-2,4(1H,3H)-dione derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors. Bioorg. Med. Chem.,  2015, 23(4), 681-693.
 [http://dx.doi.org/10.1016/j.bmc.2014.12.071] [PMID:  25614115]

[36]
Kulkarni, S.S.; Singh, S.; Shah, J.R.; Low, W.K.; Talele, T.T. Synthesis and SAR optimization of quinazolin-4(3H)-ones as poly(ADP-ribose)polymerase-1 inhibitors. Eur. J. Med. Chem.,  2012, 50, 264-273.
 [http://dx.doi.org/10.1016/j.ejmech.2012.02.001] [PMID:  22365563]

[37]
Boraei, A.T.A.; Singh, P.K.; Sechi, M.; Satta, S. Discovery of novel functionalized 1,2,4-triazoles as PARP-1 inhibitors in breast cancer: Design, synthesis and antitumor activity evaluation. Eur. J. Med. Chem.,  2019, 182, 111621.
 [http://dx.doi.org/10.1016/j.ejmech.2019.111621] [PMID:  31442685]

[38]
Chadha, N.; Jaggi, A.S.; Silakari, O. Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors. Mol. Divers.,  2017, 21(3), 655-660.
 [http://dx.doi.org/10.1007/s11030-017-9754-7] [PMID:  28653128]

[39]
Chadha, N.; Silakari, O. Identification of low micromolar dual inhibitors for aldose reductase (ALR2) and poly (ADP-ribose) polymerase (PARP-1) using structure based design approach. Bioorg. Med. Chem. Lett.,  2017, 27(11), 2324-2330.
 [http://dx.doi.org/10.1016/j.bmcl.2017.04.038] [PMID:  28438542]

[40]
Hewlett, E.; Toma, M.; Sullivan-Reed, K.; Gordo, J.; Sliwinski, T.; Tulin, A.; Childers, W.E.; Skorski, T. Novel allosteric PARP1 inhibitors for the treatment of BRCA-deficient leukemia. Med. Chem. Res.,  2020, 29(6), 962-978.
 [http://dx.doi.org/10.1007/s00044-020-02537-0] [PMID:  33071527]

[41]
Upton, K.; Meyers, M.; Thorsell, A.G.; Karlberg, T.; Holechek, J.; Lease, R.; Schey, G.; Wolf, E.; Lucente, A.; Schüler, H.; Ferraris, D. Design and synthesis of potent inhibitors of the mono(ADP-ribosyl)transferase, PARP14. Bioorg. Med. Chem. Lett.,  2017, 27(13), 2907-2911.
 [http://dx.doi.org/10.1016/j.bmcl.2017.04.089] [PMID:  28495083]

[42]
Holechek, J.; Lease, R.; Thorsell, A.G.; Karlberg, T.; McCadden, C.; Grant, R.; Keen, A.; Callahan, E.; Schüler, H.; Ferraris, D.; Ferraris, D. Design, synthesis and evaluation of potent and selective inhibitors of mono-(ADP-ribosyl)transferases PARP10 and PARP14. Bioorg. Med. Chem. Lett.,  2018, 28(11), 2050-2054.
 [http://dx.doi.org/10.1016/j.bmcl.2018.04.056] [PMID:  29748053]

[43]
Ramadan, S.K.; Elrazaz, E.Z.; Abouzid, K.A.M.; El-Naggar, A.M. Design, synthesis and in silico studies of new quinazolinone derivatives as antitumor PARP-1 inhibitors. RSC Advances,  2020, 10(49), 29475-29492.
 [http://dx.doi.org/10.1039/D0RA05943A] [PMID:  35521104]

[44]
Chen, J.; Peng, H.; He, J.; Huan, X.; Miao, Z.; Yang, C. Synthesis of isoquinolinone-based tricycles as novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. Bioorg. Med. Chem. Lett.,  2014, 24(12), 2669-2673.
 [http://dx.doi.org/10.1016/j.bmcl.2014.04.061] [PMID:  24815508]

[45]
Suyavaran, A.; Ramamurthy, C.; Mareeswaran, R.; Shanthi, Y.V.; Selvakumar, J.; Mangalaraj, S.; Kumar, M.S.; Ramanathan, C.R.; Thirunavukkarasu, C. Synthesis and biological evaluation of isoindoloisoquinolinone, pyroloisoquinolinone and benzoquinazolinone derivatives as poly(ADP-ribose) polymerase-1 inhibitors. Bioorg. Med. Chem.,  2015, 23(3), 488-498.
 [http://dx.doi.org/10.1016/j.bmc.2014.12.017] [PMID:  25555733]

[46]
Velagapudi, U.K.; Langelier, M.F.; Delgado-Martin, C.; Diolaiti, M.E.; Bakker, S.; Ashworth, A.; Patel, B.A.; Shao, X.; Pascal, J.M.; Talele, T.T. Design and synthesis of Poly(ADP-ribose) polymerase inhibitors: Impact of adenosine pocket-binding motif appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on potency and selectivity. J. Med. Chem.,  2019, 62(11), 5330-5357.
 [http://dx.doi.org/10.1021/acs.jmedchem.8b01709] [PMID:  31042381]

[47]
Patel, M.R.; Bhatt, A.; Steffen, J.D.; Chergui, A.; Murai, J.; Pommier, Y.; Pascal, J.M.; Trombetta, L.D.; Fronczek, F.R.; Talele, T.T. Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors. J. Med. Chem.,  2014, 57(13), 5579-5601.
 [http://dx.doi.org/10.1021/jm5002502] [PMID:  24922587]

[48]
Gangloff, A.R.; Brown, J.; de Jong, R.; Dougan, D.R.; Grimshaw, C.E.; Hixon, M.; Jennings, A.; Kamran, R.; Kiryanov, A.; O’Connell, S.; Taylor, E.; Vu, P. Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors. Bioorg. Med. Chem. Lett.,  2013, 23(16), 4501-4505.
 [http://dx.doi.org/10.1016/j.bmcl.2013.06.055] [PMID:  23850199]

[49]
Shao, X.; Pak, S.; Velagapudi, U.K.; Gobbooru, S.; Kommaraju, S.S.; Low, W.K.; Subramaniam, G.; Pathak, S.K.; Talele, T.T. Synthesis of 2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamide and 3-oxo-3,4-dihydrobenzo[b][1,4]oxazine-8-carboxamide derivatives as PARP1 inhibitors. Bioorg. Chem.,  2020, 102, 104075.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104075] [PMID:  32777641]

[50]
Zhou, D.; Chu, W.; Xu, J.; Jones, L.A.; Peng, X.; Li, S.; Chen, D.L.; Mach, R.H. Synthesis, [¹ö F] radiolabeling, and evaluation of
poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors for in vivo
imaging of PARP-1 using positron emission tomography. Bioorg. Med. Chem.,  2014, 22(5), 1700-1707.
 [http://dx.doi.org/10.1016/j.bmc.2014.01.019] [PMID:  24503274]

[51]
Li, H.; Hu, Y.; Wang, X.; He, G.; Xu, Y.; Zhu, Q. 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.
 [http://dx.doi.org/10.1016/j.bmc.2016.08.016] [PMID:  27561983]

[52]
Xie, Z.; Zhou, Y.; Zhao, W.; Jiao, H.; Chen, Y.; Yang, Y.; Li, Z. Identification of novel PARP-1 inhibitors: Drug design, synthesis and biological evaluation. Bioorg. Med. Chem. Lett.,  2015, 25(20), 4557-4561.
 [http://dx.doi.org/10.1016/j.bmcl.2015.08.060] [PMID:  26342868]

[53]
Xie, Z.; Chen, Y.; Xu, P.; Zhou, Y.; Lai, F.; Chen, X.; Xu, B. Design, synthesis and bioevaluation of 1: H-indole-4-carboxamide derivatives as potent poly(ADP-ribose) polymerase-1 inhibitors. RSC Advances,  2016, 6(84), 80784-80796.
 [http://dx.doi.org/10.1039/C6RA12591C]

[54]
Li, S.; Li, X.Y.; Zhang, T.J.; Kamara, M.O.; Liang, J.W.; Zhu, J.; Meng, F.H. Design, synthesis and biological evaluation of homoerythrina alkaloid derivatives bearing a triazole moiety as PARP-1 inhibitors and as potential antitumor drugs. Bioorg. Chem.,  2020, 94, 103385.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103385] [PMID:  31669094]

[55]
Zheng, M.; Mex, M.; Götz, K.H.; Marx, A. Synthesis of disaccharide nucleoside analogues as potential poly(ADP-ribose) polymerase-1 inhibitors. Org. Biomol. Chem.,  2018, 16(46), 8904-8907.
 [http://dx.doi.org/10.1039/C8OB01894D] [PMID:  30203829]

[56]
He, X.; Li, X-Y.; Liang, J-W.; Cao, C.; Li, S.; Zhang, T-J.; Meng, F-H. Design, synthesis and anticancer activities evaluation of novel 5H-dibenzo[b,e]azepine-6,11-dione derivatives containing 1,3,4-oxadiazole units. Bioorg. Med. Chem. Lett.,  2018, 28(5), 847-852.
 [http://dx.doi.org/10.1016/j.bmcl.2018.02.008] [PMID:  29456106]

[57]
El-Mongy, E.I.; Khedr, M.A.; Taleb, N.A.; Awad, H.M.; Abbas, S.E-S. Design, Synthesis, and Biological Evaluation of some Cyclohepta[b]Thiophene and substituted Pentahydrocycloheptathieno[2,3-d]pyrimidine derivatives. J. Heterocycl. Chem.,  2017, 54(2), 1084-1093.
 [http://dx.doi.org/10.1002/jhet.2678]

[58]
Wang, L.; Liu, F.; Jiang, N.; Zhou, W.; Zhou, X.; Zheng, Z. Design, synthesis, and biological evaluation of novel PARP-1 inhibitors based on a 1H-thieno[3,4-d] imidazole-4-carboxamide scaffold. Molecules,  2016, 21(6), 772.
 [http://dx.doi.org/10.3390/molecules21060772] [PMID:  27304949]

[59]
Fu, L.; Wang, S.; Wang, X.; Wang, P.; Zheng, Y.; Yao, D.; Guo, M.; Zhang, L.; Ouyang, L. Crystal structure-based discovery of a novel synthesized PARP1 inhibitor (OL-1) with apoptosis-inducing mechanisms in triple-negative breast cancer. Sci. Rep.,  2016, 6(1), 3.
 [http://dx.doi.org/10.1038/s41598-016-0007-2] [PMID:  28442756]

[60]
Wang, B.; Chu, D.; Feng, Y.; Shen, Y.; Aoyagi-Scharber, M.; Post, L.E. Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. J. Med. Chem.,  2016, 59(1), 335-357.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b01498] [PMID:  26652717]

[61]
Wang, J.; Tan, H.; Sun, Q.; Ge, Z.; Wang, X.; Wang, Y.; Li, R. Design, synthesis and biological evaluation of pyridazino[3,4,5-de]quinazolin-3(2H)-one as a new class of PARP-1 inhibitors. Bioorg. Med. Chem. Lett.,  2015, 25(11), 2340-2344.
 [http://dx.doi.org/10.1016/j.bmcl.2015.04.013] [PMID:  25899312]

[62]
Cincinelli, R.; Musso, L.; Merlini, L.; Giannini, G.; Vesci, L.; Milazzo, F.M.; Carenini, N.; Perego, P.; Penco, S.; Artali, R.; Zunino, F.; Pisano, C.; Dallavalle, S. 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. Bioorg. Med. Chem.,  2014, 22(3), 1089-1103.
 [http://dx.doi.org/10.1016/j.bmc.2013.12.031] [PMID:  24398383]

[63]
Zhu, Q.; Wang, X.; Chu, Z.; He, G.; Dong, G.; Xu, Y. Design, synthesis and biological evaluation of novel imidazo[4,5-c]pyridinecarboxamide derivatives as PARP-1 inhibitors. Bioorg. Med. Chem. Lett.,  2013, 23(7), 1993-1996.
 [http://dx.doi.org/10.1016/j.bmcl.2013.02.032] [PMID:  23481647]

[64]
Reilly, S.W.; Puentes, L.N.; Schmitz, A.; Hsieh, C.J.; Weng, C.C.; Hou, C.; Li, S.; Kuo, Y.M.; Padakanti, P.; Lee, H.; Riad, A.A.; Makvandi, M.; Mach, R.H. Synthesis and evaluation of an AZD2461 [18F]PET probe in non-human primates reveals the PARP-1 inhibitor to be non-blood-brain barrier penetrant. Bioorg. Chem.,  2019, 83, 242-249.
 [http://dx.doi.org/10.1016/j.bioorg.2018.10.015] [PMID:  30390553]

[65]
Tok, F. Koçyi̇Ği̇T-Kaymakçioğlu, B.; İLhan, R.; Yilmaz, S.; Ballar-Kirmizibayrak, P.; Taşkin-Tok, T. Design, synthesis, biological evaluation and molecular docking of novel molecules to PARP-1 enzyme. Turk. J. Chem.,  2019, 43, 1290-1305.
 [http://dx.doi.org/10.3906/kim-1905-15]

[66]
Ryu, H.; Ahn, J.; Choi, H.K. Novel benzamide derivatives: Synthesis and bioactivity as potent PARP-1 inhibitors. Bull. Korean Chem. Soc.,  2017, 38(8), 935-943.
 [http://dx.doi.org/10.1002/bkcs.11207]

[67]
Wang, B.; Qian, H.; Yiu, S.M.; Sun, J.; Zhu, G. Platinated benzonaphthyridone is a stronger inhibitor of poly(ADP-ribose) polymerase-1 and a more potent anticancer agent than is the parent inhibitor. Eur. J. Med. Chem.,  2014, 71, 366-373.
 [http://dx.doi.org/10.1016/j.ejmech.2013.10.062] [PMID:  24361480]

Rights & Permissions Print Cite

Article Metrics

3

Explore Articles

Open Access

Open Access Articles

DOI https://dx.doi.org/10.2174/1570180819666220615090709	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X

Letters in Drug Design & Discovery

Synthetic PARP-1 Inhibitors Reported During the Last Decade

Abstract Play Pause

Abstract