{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T21:59:51Z","timestamp":1783288791240,"version":"3.54.6"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T00:00:00Z","timestamp":1677974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100019310","name":"Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study","doi-asserted-by":"publisher","award":["0223\u20100002\u20100002000\u201044"],"award-info":[{"award-number":["0223\u20100002\u20100002000\u201044"]}],"id":[{"id":"10.13039\/501100019310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Poly (ADP\u2010ribose) polymerase\u20101 (PARP\u20101) inhibitors have been successfully applied in the clinical treatment of various cancer. Side effects and drug resistant cases were reported, and more effective PARP\u20101 inhibitors were required. However, studies on the AD site of PARP\u20101 inhibitors are currently incomplete. Therefore, to synthesize more potential candidate PARP\u20101 inhibitors and disclose some AD site SAR of the PARP\u20101 inhibitors, herein, a series of 2\u2010phenyl\u2010benzimidazole\u20104\u2010carboxamide derivatives using different saturated nitrogen\u2010contained heterocycles as linker group (<jats:bold>6a\u20106t<\/jats:bold>) have been designed, synthesized, and evaluated PARP\u20101 inhibitory activity and proliferation inhibitory against BRCA\u20101 mutant MDA\u2010MB\u2010436 cell line in vitro. The results showed <jats:bold>6b<\/jats:bold> (IC50\u00a0=\u00a08.65\u2009nM) exhibited the most PARP\u20101 enzyme inhibitory activity comparable with Veliparib (IC50\u00a0=\u00a015.54\u2009nM) and Olaparib (IC50\u00a0=\u00a02.77\u2009nM); <jats:bold>6m<\/jats:bold> exhibited the strongest MDA\u2010MB\u2010436 cell anti\u2010proliferation activity (IC50\u00a0=\u00a025.36\u2009\u00b1\u20096.06\u2009\u03bcM) comparable with Olaparib (IC50\u00a0=\u00a023.89\u2009\u00b1\u20093.81\u2009\u03bcM). The compounds <jats:bold>6b<\/jats:bold>, <jats:bold>6r<\/jats:bold>, and <jats:bold>6m<\/jats:bold> could be potential candidates for effective PARP\u20101 inhibitors and valuable for further optimization. The analysis of activity data also showed that the holistically anti\u2010proliferation activity of the 1,4\u2010diazepane group was about~twofold than that of the piperazine group. Meanwhile, the terminal 3\u2010methyl\u2010furanyl group exhibited the most robust PARP\u20101 inhibitory and anti\u2010proliferation activity. It is hoped that the results could benefitable for further optimization of PARP\u20101 inhibitors. Furthermore, we note that some compounds (<jats:bold>6d<\/jats:bold>,<jats:bold>6g<\/jats:bold>,<jats:bold>6n<\/jats:bold>,<jats:bold>6p<\/jats:bold>,<jats:bold>6s<\/jats:bold>) showed poor PARP\u20101 inhibitory (&gt;500\u2009nM) but relatively good anti\u2010proliferation activity, which indicates the proliferation inhibitory mechanism against MDA\u2010MB\u2010436 cell line was worth investigating in\u2010depth.<\/jats:p>","DOI":"10.1111\/cbdd.14216","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T14:33:11Z","timestamp":1675866791000},"page":"1335-1347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Design, synthesis, and evaluation of 1<i>H<\/i>\u2010benzo[d]imidazole\u20104\u2010carboxamide <scp>PARP<\/scp>\u20101 inhibitors using different saturated nitrogen\u2010contained heterocycle as linker group"],"prefix":"10.1111","volume":"101","author":[{"given":"Kaiyue","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaojia","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Chemistry Tsinghua University  Beijing China"},{"name":"The State Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology (Ministry of Education) Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Pharmacology, Hunan Province, Cooperative Innovation Center for Molecular Target New Drug Study, College of Pharmacy, Hengyang Medical School University of South China  Hengyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.01.034"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033\u2010021\u201006285\u20101"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010011\u20100811\u20106"},{"issue":"7","key":"e_1_2_8_5_1","first-page":"2711","article-title":"Identification of potent nontoxic poly(ADP\u2010Ribose) polymerase\u20101 inhibitors: Chemopotentiation and pharmacological studies","volume":"9","author":"Calabrese C. 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