{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:58:42Z","timestamp":1784080722740,"version":"3.55.0"},"reference-count":72,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["16-33-60604"],"award-info":[{"award-number":["16-33-60604"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A series of A-ring modified oleanolic and ursolic acid derivatives including C28 amides (3-oxo-C2-nicotinoylidene\/furfurylidene, 3\u03b2-hydroxy-C2-nicotinoylidene, 3\u03b2-nicotinoyloxy-, 2-cyano-3,4-seco-4(23)-ene, indolo-, lactame and azepane) were synthesized and screened for their cytotoxic activity against the NCI-60 cancer cell line panel. The results of the first assay of thirty-two tested compounds showed that eleven derivatives exhibited cytotoxicity against cancer cells, and six of them were selected for complete dose\u2013response studies. A systematic study of local SARs has been carried out by comparative analysis of potency distributions and similarity relationships among the synthesized compounds using network-like similarity graphs. Among the oleanane type triterpenoids, C2-[4-pyridinylidene]-oleanonic C28-morpholinyl amide exhibited sub-micromolar potencies against 15 different tumor cell lines and revealed particular selectivity for non-small cell lung cancer (HOP-92) with a GI50 value of 0.0347 \u03bcM. On the other hand, superior results were observed for C2-[3-pyridinylidene]-ursonic N-methyl-piperazinyl amide 29, which exhibited a broad-spectrum inhibition activity with GI50 &lt; 1 \u03bcM against 33 tumor cell lines and &lt;2 \u03bcM against all 60 cell lines. This compound has been further evaluated for cell cycle analysis to decipher the mechanism of action. The data indicate that compound 29 could exhibit both cytostatic and cytotoxic activity, depending on the cell line evaluated. The cytostatic activity appears to be determined by induction of the cell cycle arrest at the S (MCF-7, SH-SY5Y cells) or G0\/G1 phases (A549 cells), whereas cytotoxicity of the compound against normal cells is nonspecific and arises from apoptosis without significant alterations in cell cycle distribution (HEK293 cells). Our results suggest that the antiproliferative effect of compound 29 is mediated through ROS-triggered apoptosis that involves mitochondrial membrane potential depolarization and caspase activation.<\/jats:p>","DOI":"10.3390\/ijms22189796","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T10:31:34Z","timestamp":1631269894000},"page":"9796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Novel A-Ring Chalcone Derivatives of Oleanolic and Ursolic Amides with Anti-Proliferative Effect Mediated through ROS-Triggered Apoptosis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-6063","authenticated-orcid":false,"given":"Elmira","family":"Khusnutdinova","sequence":"first","affiliation":[{"name":"Ufa Institute of Chemistry UFRC RAS, 71 pr. Oktyabrya, 450054 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-6805","authenticated-orcid":false,"given":"Anastasiya","family":"Petrova","sequence":"additional","affiliation":[{"name":"Ufa Institute of Chemistry UFRC RAS, 71 pr. Oktyabrya, 450054 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulfia","family":"Zileeva","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics UFRC RAS, 71 pr. Oktyabrya, 450054 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-7895","authenticated-orcid":false,"given":"Ulyana","family":"Kuzmina","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics UFRC RAS, 71 pr. Oktyabrya, 450054 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana","family":"Zainullina","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics UFRC RAS, 71 pr. Oktyabrya, 450054 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-8261","authenticated-orcid":false,"given":"Yulia","family":"Vakhitova","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics UFRC RAS, 71 pr. 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WHO Traditional Medicine Strategy: 2014\u20132023, WHO Press."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Che, C.-T., and Zhang, H. (2019). Plant Natural Products for Human Health. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040830"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1055\/a-0832-2383","article-title":"Natural Product Triterpenoids and Their Semi-Synthetic Derivatives with Potential Anticancer Activity","volume":"85","author":"Ren","year":"2019","journal-title":"Planta Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Soica, C., Danciu, C., Savoiu-Balint, G., Borcan, F., Ambrus, R., Zupko, I., Bojin, F., Coricovac, D., Ciurlea, S., and Avram, S. (2014). Betulinic acid in complex with a gamma-cyclodextrin derivative decreases proliferation and in vivo tumor development of non-metastatic and metastatic B164A5 cells. Int. J. Mol. Sci., 15.","DOI":"10.3390\/ijms15058235"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejmech.2017.07.013","article-title":"Oleanane-, ursane-, and quinone methide friedelane-type triterpenoid derivatives: Recent advances in cancer treatment","volume":"142","author":"Salvador","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.2174\/0929867324666170818111933","article-title":"Known Triterpenes and their Derivatives as Scaffolds for the Development of New Therapeutic Agents for Cancer","volume":"25","author":"Peron","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Borella, R., Forti, L., Gibellini, L., De Gaetano, A., De Biasi, S., Nasi, M., Cossarizza, A., and Pinti, M. (2019). Synthesis and Anticancer Activity of CDDO and CDDO-Me, Two Derivatives of Natural Triterpenoids. Molecules, 24.","DOI":"10.3390\/molecules24224097"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0960-894X(02)00105-1","article-title":"A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production","volume":"12","author":"Honda","year":"2002","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1158\/0008-5472.CAN-06-4534","article-title":"The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A\/J mice","volume":"67","author":"Liby","year":"2007","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9965","DOI":"10.1021\/acs.jmedchem.0c01088","article-title":"CDDO-imidazolide Targets Multiple Amino Acid Residues on the Nrf2 Adaptor, Keap1","volume":"63","author":"Meng","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"96","DOI":"10.4161\/cbt.9.2.10287","article-title":"Downregulation of c-FLIP, XIAP and Mcl-1 protein as well as depletion of reduced glutathione contribute to the apoptosis induction of glycyrrhetinic acid derivatives in leukemia cells","volume":"9","author":"Song","year":"2010","journal-title":"Cancer Biol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11541","DOI":"10.1016\/j.tet.2008.10.035","article-title":"Chemical modifications of natural triterpenes-glycyrrhetinic and boswellic acids: Evaluation of their biological activity","volume":"64","author":"Subba","year":"2008","journal-title":"Tetrahedron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1016\/j.bmcl.2008.03.031","article-title":"Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives","volume":"18","author":"Chadalapaka","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Markov, A.V., Odarenko, K.V., Sen\u2019kova, A.V., Salomatina, O.V., Salakhutdinov, N.F., and Zenkova, M.A. (2020). Cyano Enone-Bearing Triterpenoid Soloxolone Methyl Inhibits Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma Cells In Vitro and Metastasis of Murine Melanoma In Vivo. Molecules, 25.","DOI":"10.3390\/molecules25245925"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5192","DOI":"10.1039\/C4OB00679H","article-title":"An efficient synthesis of methyl 2-cyano-3,12-dioxoursol-1,9-dien-28-oate (CDDU-methyl ester): Analogues, biological activities, and comparison with oleanolic acid derivatives","volume":"12","author":"Fu","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bartona, D.H.R., Head, J., and May, P.J. (1957). Long-range effects in alicyclic systems. Part II. The rates of condensation of some triterpenoid ketones with benzaldehyde. J. Chem. Soc., 935\u2013944.","DOI":"10.1039\/jr9570000935"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104692","DOI":"10.1016\/j.bioorg.2021.104692","article-title":"Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents","volume":"109","author":"Wu","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1007\/s00044-019-02349-x","article-title":"Synthesis and biological evaluation of ursolic acid derivatives containing an aminoguanidine moiety","volume":"28","author":"Wu","year":"2019","journal-title":"Med. Chem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sousa, J.L.C., Gon\u00e7alves, C., Ferreira, R.M., Cardoso, S.M., Freire, C.S.R., Silvestre, A.J.D., and Silva, A.M.S. (2021). Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants. Antioxidants, 10.","DOI":"10.3390\/antiox10020148"},{"key":"ref_20","unstructured":"Naglah, A.M., El-Galil, A.B.D.E.A.M.R., and Al-Omar, M.A. (2018). Oleanolic Acid Methyl Ester Derivatives. (US-9969768-B1), U.S. Patent."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10862","DOI":"10.1039\/C3RA46492J","article-title":"Synthesis and biologic evaluation of oleanolic acid derivative-chalcone conjugates as a-glucosidase inhibitors","volume":"4","author":"Chu","year":"2014","journal-title":"RSC Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.2337\/db12-1215","article-title":"Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes","volume":"62","author":"Castellano","year":"2013","journal-title":"Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/10286020903405456","article-title":"Synthesis and alpha-glucosidase inhibitory activity of oleanolic acid derivatives","volume":"12","author":"Qian","year":"2010","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ejmech.2017.04.062","article-title":"Synthesis of novel benzylidene analogues of betulinic acid as potent cytotoxic agents","volume":"135","author":"Gupta","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Khusnutdinova, E., Galimova, Z., Lobov, A., Baikova, I., Kazakova, O., Thu, H.N.T., Tuyen, N.V., Gatilov, Y., Csuk, R., and Serbian, I. (2021). Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential. Nat. Prod. Res., 1\u201310.","DOI":"10.1080\/14786419.2021.1922904"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111964","DOI":"10.1016\/j.ejmech.2019.111964","article-title":"Synthesis and anti-cancer activity studies of dammarane-type triterpenoid derivatives","volume":"187","author":"Ma","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1900111","DOI":"10.1002\/cbdv.201900111","article-title":"Synthesis and Antitumor Evaluation in Vitro of NO-Donating Ursolic Acid-Benzylidene Derivatives","volume":"16","author":"Zhang","year":"2019","journal-title":"Chem. Biodivers."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ejmech.2013.04.009","article-title":"Synthesis and in vitro anticancer studies of novel C-2 arylidene congeners of lantadenes","volume":"64","author":"Tailor","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ejmech.2019.04.059","article-title":"Ursolic acid derivative induces apoptosis in glioma cells through down-regulation of cAMP","volume":"176","author":"Fan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2000448","DOI":"10.1002\/ardp.202000448","article-title":"Synthesis and antitumor potential of new arylidene ursolic acid derivatives via caspase-8 activation","volume":"354","author":"He","year":"2021","journal-title":"Arch. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Khwaza, V., Mlala, S., Oyedeji, O.O., and Aderibigbe, B.A. (2021). Pentacyclic triterpenoids with nitrogen-containing heterocyclic moiety, privileged hybrids in anticancer drug discovery. Molecules, 26.","DOI":"10.3390\/molecules26092401"},{"key":"ref_32","first-page":"665","article-title":"Synthesis and cytotoxicity of 28-N-propargylaminoalkylated 2,3-indolotriterpenic acids","volume":"13","author":"Khusnutdinova","year":"2018","journal-title":"Nat. Prod. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1134\/S1068162018010090","article-title":"The synthesis and selective cytotoxicity of new Mannich bases derivatives of 19- and 28-alkynyltriterpenoids","volume":"1","author":"Khusnutdinova","year":"2018","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kazakova, O.B., Giniyatullina, G.V., Mustafin, A.G., Babkov, D.A., Sokolova, E.V., and Spasov, A.A. (2020). Evaluation of cytotoxicity and \u03b1-glucosidase inhibitory activity of amide and polyamino-derivatives of lupane triterpenoids. Molecules, 25.","DOI":"10.3390\/molecules25204833"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kazakova, O., Smirnova, I., Tret\u2019yakova, E., Csuk, R., Hoenke, S., and Fischer, L. (2021). Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-Seco-Triterpenoids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041714"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.bmcl.2019.02.020","article-title":"The potential of click reactions for the synthesis of bioactive triterpenes","volume":"29","author":"Csuk","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"111653","DOI":"10.1016\/j.ejmech.2019.111653","article-title":"Design and synthesis of pentacyclic triterpene conjugates and their use in medicinal research","volume":"182","author":"Hodon","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1021\/acs.jnatprod.8b00864","article-title":"Madecassic Acid Derivatives as Potential Anticancer Agents: Synthesis and Cytotoxic Evaluation","volume":"82","author":"Valdeira","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3389\/fchem.2018.00434","article-title":"Synthesis and Biological Evaluation of New Madecassic Acid Derivatives Targeting ERK Cascade Signaling","volume":"6","author":"Valdeira","year":"2018","journal-title":"Front. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/ddr.430340203","article-title":"Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen","volume":"34","author":"Boyd","year":"1995","journal-title":"Drug Dev. Res."},{"key":"ref_41","first-page":"826","article-title":"Evidence for prostanoid biosynthesis as a biochemical feature of certain subclasses of non-small cell carcinomas of the lung as determined in established cell lines derived from human lung tumors","volume":"49","author":"Hubbard","year":"1989","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/jnci\/83.11.757","article-title":"Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines","volume":"83","author":"Monks","year":"1991","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1126\/science.275.5298.343","article-title":"An information-intensive approach to the molecular pharmacology of cancer","volume":"275","author":"Weinstein","year":"1997","journal-title":"Science"},{"key":"ref_44","first-page":"622","article-title":"The National Cancer Institute: Cancer drug discovery and development program","volume":"19","author":"Grever","year":"1992","journal-title":"Semin. Oncol."},{"key":"ref_45","unstructured":"Collins, J.M. (2014, September 23). Developmental Therapeutics Program NCI\/NIH, Available online: http:\/\/dtp.cancer.gov\/branches\/btb\/ivclsp.html."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18656","DOI":"10.3390\/molecules191118656","article-title":"Synthesis and in vitro antitumor activity of a novel series of 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline fragment","volume":"19","author":"Montoya","year":"2014","journal-title":"Molecules"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0378-4274(95)03474-9","article-title":"Signalling mechanisms and oxidative stress in apoptosis","volume":"82","author":"Slater","year":"1995","journal-title":"Toxicol. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.cbi.2008.05.029","article-title":"Cytotoxic and genotoxic effects of tambjamine D, an alkaloid isolated from the nudibranch Tambja eliora, on Chinese hamster lung fibroblasts","volume":"174","author":"Cavalcanti","year":"2008","journal-title":"Chem. Biol. Interact."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, G.W., Lv, C., Shi, Z.R., Zeng, R.T., Dong, X.Y., Zhang, W.D., Liu, R.H., Shan, L., and Shen, Y.H. (2014). Abieslactone induces cell cycle arrest and apoptosis in human hepatocellular carcinomas through the mitochondrial pathway and the generation of reactive oxygen species. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115151"},{"key":"ref_50","first-page":"15","article-title":"Molecular signaling in death receptor and mitochondrial pathways of apoptosis (Review)","volume":"22","author":"Gupta","year":"2003","journal-title":"Int. J. Oncol."},{"key":"ref_51","first-page":"a006080","article-title":"Cell Death Signaling. Cold Spring Harb","volume":"7","author":"Green","year":"2015","journal-title":"Perspect. Biol."},{"key":"ref_52","first-page":"4375","article-title":"Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: Correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1","volume":"63","author":"Shishodia","year":"2003","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00109-011-0746-2","article-title":"Ursolic acid inhibits multiple cell survival pathways leading to suppression of growth of prostate cancer xenograft in nude mice","volume":"89","author":"Shanmugam","year":"2011","journal-title":"J. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6075","DOI":"10.1021\/jm800867g","article-title":"Structure-activity relationship anatomy by network-like similarity graphs and local structure-activity relationship indices","volume":"51","author":"Wawer","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1021\/ci500588j","article-title":"DataWarrior: An open-source program for chemistry aware data visualization and analysis","volume":"55","author":"Sander","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1158\/0008-5472.CAN-12-1370","article-title":"CellMiner: A web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set","volume":"72","author":"Reinhold","year":"2012","journal-title":"Cancer Res."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.3389\/fonc.2019.01067","article-title":"Randomized Phase II Trial of Triapine-Cisplatin-Radiotherapy for Locally Advanced Stage Uterine Cervix or Vaginal Cancers","volume":"9","author":"Kunos","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/jnci\/85.4.271","article-title":"The current status of camptothecin analogues as antitumor agents","volume":"85","author":"Slichenmyer","year":"1993","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/ijc.10699","article-title":"Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest\/apoptosis and hepatocyte differentiation in human hepatoma cells","volume":"103","author":"Yamashita","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/nbt.1581","article-title":"Comprehensive characterization of cytochrome P450 isozyme selectivity across chemical libraries","volume":"27","author":"Veith","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.1021\/jm060379l","article-title":"Medicinal chemistry of hERG optimizations: Highlights and hang-ups","volume":"49","author":"Jamieson","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: A platform for systematic ADMET evaluation based on a comprehensively collected ADMET database","volume":"10","author":"Dong","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1007\/s10600-011-0050-y","article-title":"Conjugates of several lupane, oleanane, and ursane triterpenoids with the antituberculosis drug isoniazid and pyridinecarboxaldehydes","volume":"47","author":"Kazakova","year":"2011","journal-title":"Chem. Nat. Compd."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1134\/S1068162010030155","article-title":"Synthesis, modifications, and antimicrobial activity of the methylpiperazinyl amides of triterpenic acids","volume":"36","author":"Kazakova","year":"2010","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1007\/s00044-017-1972-0","article-title":"Synthesis and evaluation of 2,3-indolotriterpenoids as new \u03b1-glucosidase inhibitors","volume":"26","author":"Khusnutdinova","year":"2017","journal-title":"Med. Chem. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1134\/S1068162010060142","article-title":"Synthesis of triterpenoid acylates: Effective reproduction inhibitors of influenza A (H1N1) and papilloma viruses","volume":"36","author":"Kazakova","year":"2010","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrc1951","article-title":"The NCI60 human tumour cell line anticancer drug screen","volume":"6","author":"Shoemaker","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1158\/1535-7163.MCT-10-0106","article-title":"Analysis of Food and Drug Administration-approved anticancer agents in the NCI60 panel of human tumor cell lines","volume":"9","author":"Holbeck","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/sj.leu.2402464","article-title":"Developmental therapeutics program at the NCI: Molecular target and drug discovery process","volume":"16","author":"Monga","year":"2002","journal-title":"Leukemia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.bcp.2012.01.022","article-title":"Antiproliferative mechanisms of action of the flavin dehydrogenase inhibitors diphenylene iodonium and di-2-thienyliodonium based on molecular profiling of the NCI-60 human tumor cell panel","volume":"83","author":"Doroshow","year":"2012","journal-title":"Biochem. Pharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9796\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:32Z","timestamp":1760166032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,10]]},"references-count":72,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189796"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189796","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,10]]}}}