{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:08:42Z","timestamp":1784948922168,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,7]],"date-time":"2023-05-07T00:00:00Z","timestamp":1683417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Research Foundation of the Department of Education of Anhui Province","award":["KJ2021A1166"],"award-info":[{"award-number":["KJ2021A1166"]}]},{"name":"Natural Science Research Foundation of the Department of Education of Anhui Province","award":["KJ2019A0873"],"award-info":[{"award-number":["KJ2019A0873"]}]},{"name":"Natural Science Research Foundation of the Department of Education of Anhui Province","award":["kytd202211"],"award-info":[{"award-number":["kytd202211"]}]},{"name":"Natural Science Research Foundation of the Department of Education of Anhui Province","award":["yjs202107"],"award-info":[{"award-number":["yjs202107"]}]},{"name":"Natural Science Research Foundation of the Department of Education of Anhui Province","award":["202012216048"],"award-info":[{"award-number":["202012216048"]}]},{"name":"Natural Science Research Foundation of the Department of Education of Anhui Province","award":["201912216193"],"award-info":[{"award-number":["201912216193"]}]},{"name":"Scientific Research Team of Anui Xinhua University","award":["KJ2021A1166"],"award-info":[{"award-number":["KJ2021A1166"]}]},{"name":"Scientific Research Team of Anui Xinhua University","award":["KJ2019A0873"],"award-info":[{"award-number":["KJ2019A0873"]}]},{"name":"Scientific Research Team of Anui Xinhua University","award":["kytd202211"],"award-info":[{"award-number":["kytd202211"]}]},{"name":"Scientific Research Team of Anui Xinhua University","award":["yjs202107"],"award-info":[{"award-number":["yjs202107"]}]},{"name":"Scientific Research Team of Anui Xinhua University","award":["202012216048"],"award-info":[{"award-number":["202012216048"]}]},{"name":"Scientific Research Team of Anui Xinhua University","award":["201912216193"],"award-info":[{"award-number":["201912216193"]}]},{"name":"Pharmaceutical Institute of Anui Xinhua University","award":["KJ2021A1166"],"award-info":[{"award-number":["KJ2021A1166"]}]},{"name":"Pharmaceutical Institute of Anui Xinhua University","award":["KJ2019A0873"],"award-info":[{"award-number":["KJ2019A0873"]}]},{"name":"Pharmaceutical Institute of Anui Xinhua University","award":["kytd202211"],"award-info":[{"award-number":["kytd202211"]}]},{"name":"Pharmaceutical Institute of Anui Xinhua University","award":["yjs202107"],"award-info":[{"award-number":["yjs202107"]}]},{"name":"Pharmaceutical Institute of Anui Xinhua University","award":["202012216048"],"award-info":[{"award-number":["202012216048"]}]},{"name":"Pharmaceutical Institute of Anui Xinhua University","award":["201912216193"],"award-info":[{"award-number":["201912216193"]}]},{"name":"National Innovation and Entrepreneurship Training Program for College Students","award":["KJ2021A1166"],"award-info":[{"award-number":["KJ2021A1166"]}]},{"name":"National Innovation and Entrepreneurship Training Program for College Students","award":["KJ2019A0873"],"award-info":[{"award-number":["KJ2019A0873"]}]},{"name":"National Innovation and Entrepreneurship Training Program for College Students","award":["kytd202211"],"award-info":[{"award-number":["kytd202211"]}]},{"name":"National Innovation and Entrepreneurship Training Program for College Students","award":["yjs202107"],"award-info":[{"award-number":["yjs202107"]}]},{"name":"National Innovation and Entrepreneurship Training Program for College Students","award":["202012216048"],"award-info":[{"award-number":["202012216048"]}]},{"name":"National Innovation and Entrepreneurship Training Program for College Students","award":["201912216193"],"award-info":[{"award-number":["201912216193"]}]},{"name":"Innovation and Entrepreneurship Training Program for College Students in Anhui Province","award":["KJ2021A1166"],"award-info":[{"award-number":["KJ2021A1166"]}]},{"name":"Innovation and Entrepreneurship Training Program for College Students in Anhui Province","award":["KJ2019A0873"],"award-info":[{"award-number":["KJ2019A0873"]}]},{"name":"Innovation and Entrepreneurship Training Program for College Students in Anhui Province","award":["kytd202211"],"award-info":[{"award-number":["kytd202211"]}]},{"name":"Innovation and Entrepreneurship Training Program for College Students in Anhui Province","award":["yjs202107"],"award-info":[{"award-number":["yjs202107"]}]},{"name":"Innovation and Entrepreneurship Training Program for College Students in Anhui Province","award":["202012216048"],"award-info":[{"award-number":["202012216048"]}]},{"name":"Innovation and Entrepreneurship Training Program for College Students in Anhui Province","award":["201912216193"],"award-info":[{"award-number":["201912216193"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), the severe side effects and loss of anticancer activity caused by the lack of selectivity to cancer cells and hydrolysis of ring E prevent its clinical application. To address the issue, herein a multifunctional SN38 derivative (compound 9) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound 9 exhibited superior cytotoxicity than irinotecan against human cervical cancer HeLa cells, albeit it was inferior to SN38. More significantly, compound 9 significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound 9 had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that, compared with irinotecan, compound 9 induced similar apoptosis of cancer cells. Consequently, compound 9 can not only improve its tumor-targeting ability mediated by biotin but also exert potent anticancer activity through the effect of SN38 and valproic acid, indicating that the design concept is an effective strategy for the structural modification of SN38.<\/jats:p>","DOI":"10.3390\/molecules28093936","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T02:29:22Z","timestamp":1683512962000},"page":"3936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis and Antitumor Evaluation of Biotin-SN38-Valproic Acid Conjugates"],"prefix":"10.3390","volume":"28","author":[{"given":"Yi","family":"Dai","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Science, Anhui Xinhua University, Hefei 230088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Anhui Xinhua University, Hefei 230088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Anhui Xinhua University, Hefei 230088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bmcl.2016.12.085","article-title":"The long story of camptothecin: From traditional medicine to drugs","volume":"27","author":"Martino","year":"2017","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bocian, W., Naumczuk, B., Urbanowicz, M., Sitkowski, J., Bierczynska-Krzysik, A., Bednarek, E., Wiktorska, K., Milczarek, M., and Kozerski, L. (2021). The Mode of SN38 Derivatives Interacting with Nicked DNA Mimics Biological Targeting of Topo I Poisons. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147471"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1080\/17460441.2022.2055545","article-title":"The design and discovery of topoisomerase I inhibitors as anticancer therapies","volume":"17","author":"Selas","year":"2022","journal-title":"Expert. Opin. Drug. Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00412-005-0345-5","article-title":"Human DNA topoisomerase I: Relaxation, roles, and damage control","volume":"114","author":"Leppard","year":"2005","journal-title":"Chromosoma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113639","DOI":"10.1016\/j.ejmech.2021.113639","article-title":"Camptothecin\u2019s journey from discovery to WHO Essential Medicine: Fifty years of promise","volume":"223","author":"Khaiwa","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S243","DOI":"10.1016\/j.toxlet.2016.06.1864","article-title":"Mitigating exacerbation of Irinotecan-induced gastrointestinal toxicity in combination with an ATM inhibitor in the rat","volume":"258","author":"Cronin","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1021\/mp900243b","article-title":"Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature","volume":"7","author":"Venditto","year":"2010","journal-title":"Mol. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1021\/acs.molpharmaceut.5b00785","article-title":"Lipophilic Prodrugs of SN38: Synthesis and in Vitro Characterization toward Oral Chemotherapy","volume":"13","author":"Bala","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1039\/D1NA00838B","article-title":"An esterase-activatable prodrug formulated liposome strategy: Potentiating the anticancer therapeutic efficacy and drug safety","volume":"4","author":"Shi","year":"2022","journal-title":"Nanoscale Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.actbio.2021.10.034","article-title":"A nanotherapeutic strategy to overcome chemoresistance to irinotecan\/7-ethyl-10-hydroxy-camptothecin in colorectal cancer","volume":"137","author":"Huang","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/cmdc.202000753","article-title":"Synthesis and Biological Evaluation of 10-Substituted Camptothecin Derivatives with Improved Water Solubility and Activity","volume":"16","author":"Yang","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1080\/10717544.2021.2008053","article-title":"Synthesis and evaluation of highly releasable and structurally stable antibody-SN-38-conjugates","volume":"28","author":"Liu","year":"2021","journal-title":"Drug. Deliv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1021\/acs.jmedchem.0c00305","article-title":"Design, Synthesis, and Biological Evaluation of HSP90 Inhibitor-SN38 Conjugates for Targeted Drug Accumulation","volume":"63","author":"Zhu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1021\/acsmedchemlett.0c00131","article-title":"Artemisinin Derivatives with Antimelanoma Activity Show Inhibitory Effect against Human DNA Topoisomerase 1","volume":"11","author":"Botta","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Verza, F.A., Das, U., Fachin, A.L., Dimmock, J.R., and Marins, M. (2020). Roles of Histone Deacetylases and Inhibitors in Anticancer Therapy. Cancers, 12.","DOI":"10.3390\/cancers12061664"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Autin, P., Blanquart, C., and Fradin, D. (2019). Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors. Cancers, 11.","DOI":"10.3390\/cancers11101530"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Eckschlager, T., Plch, J., Stiborova, M., and Hrabeta, J. (2017). Histone Deacetylase Inhibitors as Anticancer Drugs. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071414"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1517\/13543784.2011.629604","article-title":"Belinostat: Clinical applications in solid tumors and lymphoma","volume":"20","author":"Molife","year":"2011","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s40265-015-0388-8","article-title":"Panobinostat: First Global Approval","volume":"75","year":"2015","journal-title":"Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1007\/s10637-022-01239-1","article-title":"Synergistic activities of the histone deacetylase inhibitors with conventional cytotoxic chemotherapies in angiosarcomas","volume":"40","author":"Zhang","year":"2022","journal-title":"Investig. New. Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cincinelli, R., Musso, L., Artali, R., Guglielmi, M.B., La Porta, I., Melito, C., Colelli, F., Cardile, F., Signorino, G., and Fucci, A. (2018). Hybrid topoisomerase I and HDAC inhibitors as dual action anticancer agents. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205018"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12072-023-10484-2","article-title":"Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma","volume":"17","author":"Ito","year":"2023","journal-title":"Hepatol. Int."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ovejero-Sanchez, M., Asensio-Juarez, G., Gonzalez, M., Puebla, P., Vicente-Manzanares, M., Pelaez, R., Gonzalez-Sarmiento, R., and Herrero, A.B. (2022). Panobinostat Synergistically Enhances the Cytotoxicity of Microtubule Destabilizing Drugs in Ovarian Cancer Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113019"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1016\/j.bmc.2018.08.008","article-title":"A series of camptothecin prodrugs exhibit HDAC inhibition activity","volume":"26","author":"Zhu","year":"2018","journal-title":"Bioorganic Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ejps.2010.06.011","article-title":"Curcumin p38-dependently enhances the anticancer activity of valproic acid in human leukemia cells","volume":"41","author":"Chen","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1111\/j.1349-7006.2008.00793.x","article-title":"Valproic acid resensitizes cisplatin-resistant ovarian cancer cells","volume":"99","author":"Lin","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_27","first-page":"417","article-title":"Valproic acid as a sensitizing agent for cancer treatment","volume":"155","year":"2019","journal-title":"Gac. Med. Mex."},{"key":"ref_28","first-page":"441","article-title":"Profound Inhibitory and Apoptotic Effects of Histone Deacetylase Inhibitor Valproic Acid on Different Cancers","volume":"6","author":"Sanaei","year":"2019","journal-title":"Crescent J. Med. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wawruszak, A., Halasa, M., Okon, E., Kukula-Koch, W., and Stepulak, A. (2021). Valproic Acid and Breast Cancer: State of the Art in 2021. Cancers, 13.","DOI":"10.3390\/cancers13143409"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jconrel.2021.09.040","article-title":"SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy","volume":"339","author":"Huang","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115377","DOI":"10.1016\/j.bmc.2020.115377","article-title":"Enhanced cellular uptake efficiency of DCM probes or SN38 conjugating with phenylboronic acids","volume":"28","author":"Zhang","year":"2020","journal-title":"Bioorganic Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1021\/acsmedchemlett.0c00031","article-title":"Folate Receptor Targeting and Cathepsin B-Sensitive Drug Delivery System for Selective Cancer Cell Death and Imaging","volume":"11","author":"Jin","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1021\/acs.molpharmaceut.8b00924","article-title":"Antibody-Assisted Delivery of a Peptide-Drug Conjugate for Targeted Cancer Therapy","volume":"16","author":"Kim","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e212","DOI":"10.1016\/j.clbc.2020.08.006","article-title":"Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer","volume":"21","author":"Andrikopoulou","year":"2021","journal-title":"Clin. Breast Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1021\/acsabm.9b00722","article-title":"Molecular Theranostic Agent with Programmed Activation for Hypoxic Tumors","volume":"2","author":"Koo","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1021\/acsabm.9b00418","article-title":"Binary Drug Reinforced First Small-Molecule-Based Prodrug for Synergistic Anticancer Effects","volume":"2","author":"Jangili","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.1039\/C5CC10367C","article-title":"Rational design of multifunctional small-molecule prodrugs for simultaneous suppression of cancer cell growth and metastasis in vitro and in vivo","volume":"52","author":"Xie","year":"2016","journal-title":"Chem. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10567","DOI":"10.1021\/acsami.7b01938","article-title":"Precise Engineering of Prodrug Cocktails into Single Polymeric Nanoparticles for Combination Cancer Therapy: Extended and Sequentially Controllable Drug Release","volume":"9","author":"Wang","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1016\/j.bmc.2017.04.025","article-title":"Dual 7-ethyl-10-hydroxycamptothecin conjugated phospholipid prodrug assembled liposomes with in vitro anticancer effects","volume":"25","author":"Du","year":"2017","journal-title":"Bioorganic Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1016\/S0960-894X(02)00388-8","article-title":"Novel 20-carbonate linked prodrugs of camptothecin and 9-aminocamptothecin designed for activation by tumour-associated plasmin","volume":"12","author":"Busscher","year":"2002","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8240","DOI":"10.1039\/D0SC01973A","article-title":"Probing biotin receptors in cancer cells with rationally designed fluorogenic squaraine dimers","volume":"11","author":"Fam","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127431","DOI":"10.1016\/j.snb.2019.127431","article-title":"Cancer cell recognition by a Cys-reactive turn-on significant enhanced fluorescent emission targeting biotin receptors","volume":"304","author":"Pei","year":"2020","journal-title":"Sens. Actuators B-Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ejmech.2018.01.001","article-title":"Biotin conjugated organic molecules and proteins for cancer therapy: A review","volume":"145","author":"Maiti","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Khoury, A., Sakoff, J.A., Gilbert, J., Karan, S., Gordon, C.P., and Aldrich-Wright, J.R. (2022). Potent Platinum(IV) Prodrugs That Incorporate a Biotin Moiety to Selectively Target Cancer Cells. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122780"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1039\/D1OB00002K","article-title":"Biotin-decorated NIR-absorbing nanosheets for targeted photodynamic cancer therapy","volume":"19","author":"Perumal","year":"2021","journal-title":"Org. Biomol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"129128","DOI":"10.1016\/j.bmcl.2023.129128","article-title":"Synthesis and biological evaluation of novel SN38-glucose conjugate for colorectal cancer treatment","volume":"81","author":"Zhang","year":"2023","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121105","DOI":"10.1016\/j.lfs.2022.121105","article-title":"Anti-tumor effects and mechanism of a novel camptothecin derivative YCJ100","volume":"311","author":"Zhang","year":"2022","journal-title":"Life Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"114610","DOI":"10.1016\/j.ejmech.2022.114610","article-title":"Design, synthesis, and biological evaluation of novel 7-substituted 10,11-methylenedioxy-camptothecin derivatives against drug-resistant small-cell lung cancer in vitro and in vivo","volume":"241","author":"Zhang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9955","DOI":"10.1021\/acs.jmedchem.2c00640","article-title":"A Mitochondria-Targeted Phenylbutyric Acid Prodrug Confers Drastically Improved Anticancer Activities","volume":"65","author":"Huang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8431","DOI":"10.1021\/ic901019p","article-title":"1,3-Diazido-2-(azidomethyl)-2-propylammonium salts","volume":"48","author":"Joo","year":"2009","journal-title":"Inorg. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19412","DOI":"10.1039\/D2RA03547B","article-title":"Late-stage ortho-C-H alkenylation of 2-arylindazoles in aqueous medium by Manganese(i)-catalysis","volume":"12","author":"Das","year":"2022","journal-title":"RSC Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1021\/acsomega.9b02786","article-title":"Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects","volume":"5","author":"Liu","year":"2019","journal-title":"ACS Omega"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"48LT01","DOI":"10.1088\/0957-4484\/27\/48\/48LT01","article-title":"Self-assembled nanoparticles comprising aptide-SN38 conjugates for use in targeted cancer therapy","volume":"27","author":"Kim","year":"2016","journal-title":"Nanotechnology"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/9\/3936\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:30:48Z","timestamp":1760124648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/9\/3936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,7]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["molecules28093936"],"URL":"https:\/\/doi.org\/10.3390\/molecules28093936","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,7]]}}}