{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:36:56Z","timestamp":1790163416174,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T00:00:00Z","timestamp":1498694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangxi Province of China","award":["2015GXNSFAA139035"],"award-info":[{"award-number":["2015GXNSFAA139035"]}]},{"name":"Science and Technology Research Projects for Universities in Guangxi Province of China","award":["YB2014278"],"award-info":[{"award-number":["YB2014278"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31060100"],"award-info":[{"award-number":["31060100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of these compounds against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), and BEL-7402 (liver) human carcinoma cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The screening results revealed that many of the compounds showed moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed similar potent inhibitory activities to the commercial anticancer drug cisplatin, while they exhibited lower cytotoxicity against normal human liver cell (HL-7702). Particularly, compound 4w, N\u2019-(3,5-difluorobenzylidene)-2-(dehydroabietyloxy)acetohydrazide, with an IC50 (50% inhibitory concentration) value of 2.21 \u03bcM against HeLa cell, was about 17-fold more active than that of the parent compound, and showed remarkable cytotoxicity with an IC50 value of 14.46 \u03bcM against BEL-7402 cell. These results provide an encouraging framework that could lead to the development of potent novel anticancer agents.<\/jats:p>","DOI":"10.3390\/molecules22071087","type":"journal-article","created":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T10:40:04Z","timestamp":1498732804000},"page":"1087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Synthesis and In Vitro Anticancer Activity of Novel Dehydroabietic Acid-Based Acylhydrazones"],"prefix":"10.3390","volume":"22","author":[{"given":"Fang-Yao","family":"Li","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China"},{"name":"College of Pharmacy, Guilin Medical University, Guilin 541004, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guilin Medical University, Guilin 541004, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Gui","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Shan","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,29]]},"reference":[{"key":"ref_1","first-page":"173","article-title":"Enhancing immune responses for cancer therapy","volume":"4","author":"Xue","year":"2007","journal-title":"Cell. Mol. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1093\/annonc\/mdw306","article-title":"Global trends and predictions in ovarian cancer mortality","volume":"27","author":"Malvezzi","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3322\/caac.21338","article-title":"Cancer statistics in China, 2015","volume":"66","author":"Chen","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1021\/np030096l","article-title":"Natural products as source of new drugs over the period","volume":"66","author":"Newman","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1021\/np900821e","article-title":"Discovery and development of natural product derived chemo-therapeutic agents based on a medicinal chemistry approach","volume":"73","author":"Lee","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1248\/cpb.53.11","article-title":"New abietane and seco-abietane diterpenes from the roots of Taiwania cryptomerioides","volume":"53","author":"Chyu","year":"2005","journal-title":"Chem. Pharm. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pertino, M.W., Vega, C., Rol\u00f3n, M., Coronel, C., Arias, A.R., and Schmeda-irschmann, G. (2017). Antiprotozoal activity of triazole derivatives of dehydroabietic acid and oleanolic acid. Molecules, 22.","DOI":"10.3390\/molecules22030369"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1248\/cpb.33.1472","article-title":"Antiulcer activity of dehydroabietic acid derivatives","volume":"33","author":"Wada","year":"1985","journal-title":"Chem. Pharm. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.bbrc.2008.02.002","article-title":"Dehydroabietic acid, a phytochemical, acts as ligand for PPARs in macrophages and adipocytes to regulate inflammation","volume":"369","author":"Kang","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1039\/c3md00151b","article-title":"Cytotoxic, immunomodulatory, antimycotic, and antiviral activities of semisynthetic 14-hydroxyabietane derivatives and triptoquinone C-4 epimers","volume":"4","author":"Zapata","year":"2013","journal-title":"Med. Chem. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.ejmech.2016.11.002","article-title":"The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: Modifications at C12 and C7","volume":"127","author":"Zhang","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bmc.2016.10.019","article-title":"Antibacterial profiling of abietane-type diterpenoids","volume":"25","author":"Helfenstein","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kusumoto1, N., Zhao, T., Swedjemark, G., Ashitani, T., Takahashi, K., and Borg-Karlson, A.K. (2014). Antifungal properties of terpenoids in Picea abies against Heterobasidion parviporum. For. Path., 44, 353\u2013361.","DOI":"10.1111\/efp.12106"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11094-006-0161-0","article-title":"Synthesis and biological activity of nitrogen-containing derivatives of methyl dehydroabietate","volume":"40","author":"Tolmacheva","year":"2006","journal-title":"Pharm. Chem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.mce.2015.05.006","article-title":"The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1","volume":"412","author":"Kim","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.phrs.2005.06.004","article-title":"Gastroprotective and cytotoxic effect of dehydroabietic acid derivatives","volume":"52","author":"Astudillo","year":"2005","journal-title":"Pharmacol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.bmcl.2015.12.038","article-title":"The synthesis and BK channel-opening activity of N-acylaminoalkyloxime derivatives of dehydroabietic acid","volume":"26","author":"Cui","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.bmcl.2016.12.032","article-title":"Identification of a diverse synthetic abietane diterpenoid library for anticancer activity","volume":"27","author":"Xu","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.bmcl.2017.01.028","article-title":"Synthesis and in vitro cytotoxic evaluation of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid","volume":"27","author":"Wen","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ejmech.2015.12.008","article-title":"Synthesis and pharmacological evaluation of dehydroabietic acid thiourea derivatives containing bisphosphonate moiety as an inducer of apoptosis","volume":"108","author":"Huang","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jinorgbio.2017.02.020","article-title":"A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson\u2019s disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies","volume":"170","author":"Cukierman","year":"2017","journal-title":"J. Inorg. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.bmc.2013.11.004","article-title":"Synthesis, molecular modeling and biological evaluation of N-benzylidene-2-((5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide derivatives as potential anticancer agents","volume":"22","author":"Zhang","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Onnis, V., Demurtas, M., Deplano, A., Balboni, G., Baldisserotto, A., Manfredini, S., Pacifico, S., Liekens, S., and Balzarini, J. (2016). Design, synthesis and evaluation of antiproliferative activity of new benzimidazolehydrazones. Molecules, 21.","DOI":"10.3390\/molecules21050579"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1016\/j.ejmech.2008.01.021","article-title":"Synthesis and structure\u2013activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives as potential agents against A549 lung cancer cells","volume":"43","author":"Xia","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1016\/j.ejmech.2010.09.007","article-title":"New class of potent antitumor acylhydrazone derivatives containing furan","volume":"45","author":"Cui","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s11030-016-9691-x","article-title":"Synthesis and antifungal activity of dehydroabietic acid-based 1,3,4-thiadiazole-thiazolidinone compounds","volume":"20","author":"Chen","year":"2016","journal-title":"Mol. Divers."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1515\/hf-2014-0315","article-title":"Synthesis and antifungal activity of dehydroabietic acid-based thiadiazole-phosphonates","volume":"69","author":"Chen","year":"2015","journal-title":"Holzforschung"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lin, G.S., Duan, W.G., Yang, L.X., Huang, M., and Lei, F.H. (2017). Synthesis and antifungal activity of novel myrtenal-based 4-methyl-1,2,4-triazole-thioethers. Molecules, 22.","DOI":"10.3390\/molecules22020193"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1515\/hf.2011.016","article-title":"Synthesis and herbicidal activity of 5-dehydroabietyl-1,3,4-oxadiazolederivatives","volume":"65","author":"Duan","year":"2011","journal-title":"Holzforschung"},{"key":"ref_30","first-page":"1114","article-title":"Synthesis and herbicidal activity of 2-substituted amino-5-dehydroabietyl-1,3,4-oxadiazole derivatives","volume":"31","author":"Mo","year":"2011","journal-title":"Chin. J. Org. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4420","DOI":"10.1007\/s00044-014-1009-x","article-title":"Synthesis and insecticidal activities of N-(5-dehydroabietyl-1,3,4-thiadiazol-2-yl)-benzene-sulfonamides","volume":"23","author":"Li","year":"2014","journal-title":"Med. Chem. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/7\/1087\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:40:50Z","timestamp":1760208050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/7\/1087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,29]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["molecules22071087"],"URL":"https:\/\/doi.org\/10.3390\/molecules22071087","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,29]]}}}