{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:11:05Z","timestamp":1775671865547,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T00:00:00Z","timestamp":1480291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["IP-2014-09-1501"],"award-info":[{"award-number":["IP-2014-09-1501"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["IP-11-2013-5660"],"award-info":[{"award-number":["IP-11-2013-5660"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"KU Leuven, Belgium","award":["GOA 10\/014"],"award-info":[{"award-number":["GOA 10\/014"]}]},{"DOI":"10.13039\/100008993","name":"University of Zagreb","doi-asserted-by":"publisher","award":["BM1.9,13.11.2.1.12"],"award-info":[{"award-number":["BM1.9,13.11.2.1.12"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008993","name":"University of Zagreb","doi-asserted-by":"publisher","award":["13.11.1.1.11."],"award-info":[{"award-number":["13.11.1.1.11."]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a\u2013k) or via a spacer (compounds 7a\u2013k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a\u2013k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a\u2013k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c\u2013e), benzodioxole (7f), p-Cl (7g) and m-CF3 (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%\u201389%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 \u03bc\u039c). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates.<\/jats:p>","DOI":"10.3390\/molecules21121629","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T10:25:22Z","timestamp":1480328722000},"page":"1629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8523-6340","authenticated-orcid":false,"given":"Kristina","family":"Pavi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Perkovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Gilja","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Kozlina","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova\u010di\u0107a 1, HR-10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Ester","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Rudjer Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, HR-10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marijeta","family":"Kralj","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Rudjer Bo\u0161kovi\u0107 Institute, Bijeni\u010dka cesta 54, HR-10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Schols","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-350X","authenticated-orcid":false,"given":"Dimitra","family":"Hadjipavlou-Litina","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, School of Pharmacy, Aristotles University of Thessaloniki, Thessaloniki 54 124, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Pontiki","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, School of Pharmacy, Aristotles University of Thessaloniki, Thessaloniki 54 124, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Zorc","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb, A. 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Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2174\/138955712801264792","article-title":"Antioxidant and antimicrobial activities of cinnamic acid derivatives","volume":"12","author":"Sova","year":"2012","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.ejmech.2004.06.013","article-title":"Esters, amides and substituted derivatives of cinnamic acid: Synthesis, antimicrobial activity and QSAR investigations","volume":"39","author":"Narasimhan","year":"2004","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7814","DOI":"10.1021\/jf0487093","article-title":"Identification of phenolics for control of Aspergillus flavus using Saccharomyces cerevisiae in a model target-gene bioassay","volume":"52","author":"Kim","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1584\/jpestics.25.263","article-title":"Fungitoxic and phytotoxic activities of cinnamic acid esters and amides","volume":"25","author":"Zhu","year":"2000","journal-title":"J. Pestic. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4059","DOI":"10.1016\/S0968-0896(03)00393-6","article-title":"Synthesis and structure-activity relationship studies of cinnamic acid-based novel thiazolidinedione antihyperglycemic agents","volume":"11","author":"Neogi","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.bmcl.2010.01.031","article-title":"Novel molecular hybrids of cinnamic acids and guanylhydrazones as potential antitubecular agents","volume":"20","author":"Bairwa","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1128\/AAC.39.10.2320","article-title":"Antimycobacterial activity of a new rifamycin derivative, 3-(4-cinnamylpiperazinyl iminomethyl) rifamycin SV (T9)","volume":"39","author":"Reddy","year":"1995","journal-title":"J. Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.bmcl.2007.11.091","article-title":"Synthesis and antimycobacterial evaluation of new trans-cinnamic acid hydrazide derivatives","volume":"18","author":"Carvalho","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1016\/j.bmcl.2011.02.022","article-title":"Design, synthesis and antimycobacterial activity of cinnamide derivatives: A molecular hybridization approach","volume":"21","author":"Kakwani","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.bmcl.2008.11.082","article-title":"Synthesis and evaluation of a novel series of pseudo-cinnamic derivatives as antituberculosis agents","volume":"19","author":"Yoya","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_14","first-page":"31","article-title":"Physicochemical characterisation of cinnamic acid derivatives. Part 1. Relationship between antioxidant activity and physicochemical properties","volume":"32","author":"Bogdashev","year":"1998","journal-title":"Pharm. Chem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1021\/jf970055t","article-title":"Antioxidant activities of caffeic acid and its related hydroxycinnamic acid compounds","volume":"45","author":"Chen","year":"1997","journal-title":"J. Agric. Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9655","DOI":"10.3390\/molecules19079655","article-title":"Novel cinnamic acid derivatives as antioxidant and anticancer agents: Design, synthesis and modeling studies","volume":"19","author":"Pontiki","year":"2014","journal-title":"Molecules"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15944","DOI":"10.1021\/bi050941u","article-title":"Novel aromatic ester from Piper longum and its analogues inhibit expression of cell adhesion molecules on endothelial cells","volume":"44","author":"Kumar","year":"2005","journal-title":"Biochemistry"},{"key":"ref_18","unstructured":"Alexander, A., and Choudhary, R.K. (1996). Process for Preparation of Sunscreen Agents. (5,527,947), U.S. Patent."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"475","DOI":"10.2174\/157340607781745410","article-title":"Trans-3-phenyl-2-propenoic acid (cinnamic acid) derivatives: Structure-activity relationship as hepatoprotective agents","volume":"3","author":"Bobadilla","year":"2007","journal-title":"Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00394-011-0227-y","article-title":"Hypolipidemic and antioxidant effects of hydroxycinnamic acids, quercetin, and cyanidin 3-glucoside in hypercholesterolemic erythrocytes (in vitro study)","volume":"51","author":"Duchnowicz","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cbi.2007.06.037","article-title":"Hypocholesterolemic and antioxidant properties of 3-(4-hydroxyl)propanoic acid derivatives in high-cholesterol fed rats","volume":"170","author":"Lee","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.neuroscience.2009.10.023","article-title":"Ferulic acid induces neural progenitor cell proliferation in vitro and in vivo","volume":"165","author":"Yabe","year":"2010","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1128\/AAC.36.5.1102","article-title":"Effects of cinnamic acid derivatives on in vitro growth of Plasmodium falciparum and on the permeability of the membrane of malaria-infected erythrocytes","volume":"36","author":"Kanaani","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6769","DOI":"10.1016\/j.bmcl.2013.10.025","article-title":"Recycling antimalarial leads for cancer: Antiproliferative properties of N-cinnamoyl chloroquine analogues","volume":"23","author":"Fernandes","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1039\/c2md20113e","article-title":"PRIMACINS, N-cinnamoyl-primaquine conjugates, with improved liver-stage antimalarial activity","volume":"3","author":"Teixeira","year":"2012","journal-title":"Med. Chem. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.bmcl.2012.12.032","article-title":"In vitro efficiency of 9-(N-cinnamoylbutyl)aminoacridines against blood- and liver-stage malaria parasites","volume":"23","author":"Teixeira","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.ejmech.2012.05.022","article-title":"Novel cinnamic acid\/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: Towards the development of potential dual action antimalarials","volume":"54","author":"Teixeira","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ejps.2012.12.003","article-title":"Overview of the therapeutic potential of piplartine (piperlongumine)","volume":"48","author":"Bezerra","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.2174\/092986711795471347","article-title":"Cinnamic acid derivatives as anticancer agents-a review","volume":"18","author":"De","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1179\/1743132812Y.0000000022","article-title":"Ozagrel for acute ischemic stroke: A meta-analysis of data from randomized controlled trials","volume":"34","author":"Zhang","year":"2012","journal-title":"Neurol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ejphar.2009.06.063","article-title":"Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies","volume":"625","author":"Solomon","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.1016\/j.ejmech.2010.05.046","article-title":"Design and synthesis of chloroquine analogs with anti-breast cancer property","volume":"45","author":"Solomon","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Van Huijsduijnen, R.H., Kiplin Guy, R., Chibale, K., Haynes, R.K., Peitz, I., Kelter, G., Phillips, M.A., Vennerstrom, J.L., Yuthavong, Y., and Wells, T.N.C. (2013). Anticancer properties of distinct antimalarial drug classes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082962"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Crespo-Ortiz, M.P., and Wei, M.Q. (2012). Antitumor activity of artemisinin and its derivatives: From a well-known antimalarial agent to a potential anticancer drug. J. Biomed. Biotechnol.","DOI":"10.1155\/2012\/247597"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/0008-5472.CAN-12-2464","article-title":"Chloroquine in cancer therapy: A double-edged sword of autophagy","volume":"73","author":"Kimura","year":"2013","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.biochi.2014.10.001","article-title":"Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis","volume":"107","author":"Ganguli","year":"2014","journal-title":"Biochimie"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/aps.2014.3","article-title":"Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell lung cancer cells in vitro","volume":"35","author":"Liu","year":"2014","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_38","first-page":"e384","article-title":"Chloroquine as a promising adjuvant chemotherapy together with sunitinib","volume":"1","author":"Kamal","year":"2014","journal-title":"Sci. Proc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4103\/2141-9248.153609","article-title":"Anticancer effect of antimalarial artemisinin compounds","volume":"5","author":"Das","year":"2015","journal-title":"Ann. Med. Health Sci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Coulter, D.W., Vennerstrom, J., Sharp, J.G., Dong, Y., Wang, X., McIntyre, E., and McGuire, T. (2015). Screening of investigational antimalarials for anticancer activity in high risk N-MYC amplified neuroblastoma (NB). Cancer Res., 75.","DOI":"10.1158\/1538-7445.AM2015-4362"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ejmech.2015.11.003","article-title":"Synthesis and in vitro antitumor evaluation of dihydroartemisinin-cinnamic acid ester derivatives","volume":"107","author":"Xu","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.drudis.2012.03.013","article-title":"Discovery of anticancer drugs from antimalarial natural products: A MEDLINE literature review","volume":"17","author":"Duffy","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.ejmech.2007.09.001","article-title":"The novel primaquine derivatives of N-alkyl, cycloalkyl or aryl urea: Synthesis, cytostatic and antiviral activity evaluations","volume":"43","author":"Zorc","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5605","DOI":"10.1016\/j.bmc.2009.06.030","article-title":"Urea and carbamate derivatives of primaquine: Synthesis, cytostatic and antioxidant activities","volume":"17","author":"Zorc","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3109\/14756366.2012.663366","article-title":"Novel 1-acyl-4-substituted semicarbazide derivatives of primaquine\u2014Synthesis, cytostatic, antiviral and antioxidative studies","volume":"28","author":"Kralj","year":"2013","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.ejmech.2014.09.013","article-title":"Novel semicarbazides and ureas of primaquine with bulky aryl or hydroxyalkyl substituents: Synthesis, cytostatic and antioxidative activity","volume":"86","author":"Kralj","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.ejmech.2016.08.021","article-title":"Novel urea and bis-urea primaquine derivatives with hydroxyphenyl and halogenphenyl substituents: Synthesis and biological evaluation","volume":"124","author":"Ester","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1021\/jm010252q","article-title":"Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff Bases of hydroxysemicarbazide as potential antitumor agents","volume":"45","author":"Ren","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_49","first-page":"335","article-title":"The novel ketoprofenamides\u2014Synthesis and spectroscopic characterization","volume":"76","author":"Zovko","year":"2003","journal-title":"Croat. Chem. Acta"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ejmech.2006.08.009","article-title":"Synthesis and in vitro antitumor effect of diclofenac and fenoprofen thiolated and nonthiolated polyaspartamide-drug conjugates","volume":"42","author":"Kralj","year":"2007","journal-title":"Eur. J. Med. Chem."},{"key":"ref_51","first-page":"328","article-title":"Cytostatic and antiviral evaluations of NSAID hydroxamic acids","volume":"73","author":"Butula","year":"2009","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1747-0285.2010.00963.x","article-title":"The novel ketoprofen amides\u2014Synthesis and biological evaluation as antioxidants, lipoxygenase inhibitors and cytostatic agents","volume":"75","author":"Pontiki","year":"2010","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejmech.2012.03.026","article-title":"Synthesis, evaluation of anticancer activity and COMPARE analysis of N-bis(tri fluoromethyl)alkyl-N\u2019-substituted ureas with pharmacophoricmoieties","volume":"53","author":"Luzina","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_54","unstructured":"Instant Cheminformatics Solutions. Available online: http:\/\/www.chemicalize.org\/."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1093\/carcin\/19.8.1393","article-title":"Inhibitors of lipoxygenase: A new class of cancer chemopreventive agents","volume":"19","author":"Rioux","year":"1998","journal-title":"Carcinogenesis (Lond.)"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0952-3278(92)90090-6","article-title":"Eicosanoids in breast cancer patients before and after mastectomy","volume":"45","author":"Kort","year":"1992","journal-title":"Prostaglandin Leukot. Essent."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/323464a0","article-title":"A novel selective broad-spectrum anti-DNA virus agent","volume":"323","author":"Rosenberg","year":"1986","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/00002030-199101000-00003","article-title":"9-(2-Phosphonylmethoxyethyl)adenine (PMEA) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys","volume":"5","author":"Balzarini","year":"1991","journal-title":"AIDS"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/12\/1629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:27:35Z","timestamp":1760210855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/21\/12\/1629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,28]]},"references-count":58,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["molecules21121629"],"URL":"https:\/\/doi.org\/10.3390\/molecules21121629","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,28]]}}}