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022161"],"award-info":[{"award-number":["\u00ba 022161"]}]},{"name":"National NMR Network (PTNMR)","award":["COMPETE 2020"],"award-info":[{"award-number":["COMPETE 2020"]}]},{"name":"FEDER","award":["2022.05718.PTDC"],"award-info":[{"award-number":["2022.05718.PTDC"]}]},{"name":"FEDER","award":["SFRH\/BD\/139760\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139760\/2018"]}]},{"name":"FEDER","award":["LA\/P\/0008\/2020"],"award-info":[{"award-number":["LA\/P\/0008\/2020"]}]},{"name":"FEDER","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"FEDER","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"FEDER","award":["\u00ba 022161"],"award-info":[{"award-number":["\u00ba 022161"]}]},{"name":"FEDER","award":["COMPETE 2020"],"award-info":[{"award-number":["COMPETE 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2020"]}]},{"name":"PIDDAC","award":["2022.05718.PTDC"],"award-info":[{"award-number":["2022.05718.PTDC"]}]},{"name":"PIDDAC","award":["SFRH\/BD\/139760\/2018"],"award-info":[{"award-number":["SFRH\/BD\/139760\/2018"]}]},{"name":"PIDDAC","award":["LA\/P\/0008\/2020"],"award-info":[{"award-number":["LA\/P\/0008\/2020"]}]},{"name":"PIDDAC","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]},{"name":"PIDDAC","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"PIDDAC","award":["\u00ba 022161"],"award-info":[{"award-number":["\u00ba 022161"]}]},{"name":"PIDDAC","award":["COMPETE 2020"],"award-info":[{"award-number":["COMPETE 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against various cancer cell lines. Methods: Twenty-two new triazole derivatives (5\u201326), of the triacetyl derivative (2) of the diterpenic lactone andrographolide (1), were synthesized via the azide-alkyne \u201cclick reaction\u201d. The antiproliferative effects of compounds 1\u201326 were evaluated using the sulforhodamine B assay against a panel of cancer cell lines and a non-tumorigenic colon cell line. A representative compound, triazole derivative 12, was further evaluated in human pancreatic ductal adenocarcinoma (PANC-1) cells for its effects on the cell cycle, apoptosis, migration, and drug synergy with 5-fluorouracil. Results: Several compounds, specifically, 9, 14, 16, and 17, bearing a phenyl moiety, exhibited improved antiproliferative activity compared to the parental compound 1. Derivative 12, selected for further investigation, induced G2\/M cell cycle arrest and apoptosis in a concentration-dependent manner. Additionally, this compound significantly reduced cell migration and demonstrated synergistic effects with 5-fluorouracil in PANC-1 cells. Conclusions: The synthesized andrographolide-based triazole derivatives, particularly compound 12, showed promising antiproliferative activity and mechanisms relevant to cancer therapy. These findings support their potential as lead compounds for further development in anticancer research.<\/jats:p>","DOI":"10.3390\/ph18050750","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:54:28Z","timestamp":1747724068000},"page":"750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Anticancer Properties of 1,2,3-Triazole-Substituted Andrographolide Derivatives"],"prefix":"10.3390","volume":"18","author":[{"given":"Joana R. L.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5895-6951","authenticated-orcid":false,"given":"Juliana","family":"Calheiros","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9328-8171","authenticated-orcid":false,"given":"Rita A. M.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3137-5329","authenticated-orcid":false,"given":"Bruno M. F.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7284-5948","authenticated-orcid":false,"given":"Carlos A. M.","family":"Afonso","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE-Associated Laboratory for Green Chemistry (LAQV) of the Network of Chemistry and Technology (REQUIMTE), Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, Universidade do Porto, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-1486","authenticated-orcid":false,"given":"Maria-Jos\u00e9 U.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41571-021-00514-z","article-title":"Planning for Tomorrow: Global Cancer Incidence and the Role of Prevention 2020\u20132070","volume":"18","author":"Soerjomataram","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jacquemin, V., Antoine, M., Dumont, J.E., Dom, G., Detours, V., and Maenhaut, C. (2022). Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications. Cancers, 14.","DOI":"10.3390\/cancers14020280"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.21037\/atm-20-7830","article-title":"Biological Properties of Andrographolide, an Active Ingredient of Andrographis Paniculata: A Narrative Review","volume":"9","author":"Vetvicka","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tundis, R., Patra, J.K., Bonesi, M., Das, S., Nath, R., Das Talukdar, A., Das, G., and Loizzo, M.R. (2023). Anti-Cancer Agent: The Labdane Diterpenoid-Andrographolide. Plants, 12.","DOI":"10.3390\/plants12101969"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wanandi, S.I., Limanto, A., Yunita, E., Syahrani, R.A., Louisa, M., Wibowo, A.E., and Arumsari, S. (2020). In Silico and in Vitro Studies on the Anti-Cancer Activity of Andrographolide Targeting Survivin in Human Breast Cancer Stem Cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240020"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16198","DOI":"10.1016\/j.phrs.2022.106198","article-title":"Andrographolide Suppresses Non-Small-Cell Lung Cancer Progression through Induction of Autophagy and Antitumor Immune Response","volume":"179","author":"Wang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.18632\/oncotarget.26628","article-title":"Andrographolide Induces DNA Damage in Prostate Cancer Cells","volume":"10","year":"2019","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.2147\/DDDT.S94983","article-title":"Andrographolide Inhibits Growth of Human T-Cell Acute Lymphoblastic Leukemia Jurkat Cells by Downregulation of PI3K\/AKT and Upregulation of P38 MAPK Pathways","volume":"10","author":"Yang","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, J., Huang, L., He, Z., Chen, M., Ding, Y., and Yao, Y. (2021). Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-\u03baB\/MiR-21-5p\/PDCD4 Signaling Pathway. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.643525"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5053","DOI":"10.1016\/j.bmc.2018.09.002","article-title":"Andrographolide Derivative as STAT3 Inhibitor That Protects Acute Liver Damage in Mice","volume":"26","author":"Chen","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tohkayomatee, R., Reabroi, S., Tungmunnithum, D., Parichatikanond, W., and Pinthong, D. (2022). Andrographolide Exhibits Anticancer Activity against Breast Cancer Cells (MCF-7 and MDA-MB-231 Cells) through Suppressing Cell Proliferation and Inducing Cell Apoptosis via Inactivation of ER-\u03b1 Receptor and PI3K\/AKT\/MTOR Signaling. Molecules, 27.","DOI":"10.3390\/molecules27113544"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12964-024-01607-9","article-title":"Potentials and Future Perspectives of Multi-Target Drugs in Cancer Treatment: The next Generation Anti-Cancer Agents","volume":"22","author":"Doostmohammadi","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ejmech.2017.05.016","article-title":"Designing Multi-Targeted Agents: An Emerging Anticancer Drug Discovery Paradigm","volume":"136","author":"Fu","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Othman, N.S., and Mohd Azman, D.K. (2022). Andrographolide Induces G2\/M Cell Cycle Arrest and Apoptosis in Human Glioblastoma DBTRG-05MG Cell Line via ERK1\/2 \/c-Myc\/P53 Signaling Pathway. Molecules, 27.","DOI":"10.3390\/molecules27196686"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2174\/1871520620666200717143109","article-title":"Andrographolide Inhibits Proliferation of Colon Cancer SW-480 Cells via Downregulating Notch Signaling Pathway","volume":"21","author":"Khan","year":"2021","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"660","DOI":"10.7150\/ijbs.19194","article-title":"Andrographolide Inhibits Angiogenesis by Inhibiting the Mir-21-5p\/TIMP3 Signaling Pathway","volume":"13","author":"Dai","year":"2017","journal-title":"Int. J. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bcp.2016.09.024","article-title":"Andrographolide Reversed 5-FU Resistance in Human Colorectal Cancer by Elevating BAX Expression","volume":"121","author":"Wang","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lakra, D.S., Bharathiraja, P., Dhanalakshmi, T., and Prasad, N.R. (2024). Andrographolide Reverts Multidrug Resistance in KBChR 8-5 Cells through AKT Signaling Pathway. Cell Biochem. Funct., 42.","DOI":"10.1002\/cbf.3948"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1039\/D3MD00711A","article-title":"Nitrogen-Containing Andrographolide Derivatives with Multidrug Resistance Reversal Effects in Cancer Cells","volume":"15","author":"Ribeiro","year":"2024","journal-title":"RSC Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5007","DOI":"10.1002\/jps.22693","article-title":"Poor Oral Bioavailability of a Promising Anticancer Agent Andrographolide Is Due to Extensive Metabolism and Efflux by P-Glycoprotein","volume":"100","author":"Ye","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1111\/1759-7714.13682","article-title":"Biodistribution of Andrographolide to Assess the Interior-Exterior Relationship between the Lung and Intestine Using MicroPET","volume":"11","author":"Zhang","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/nep.12172","article-title":"Andrographolide Induced Acute Kidney Injury: Analysis of 26 Cases Reported in Chinese Literature","volume":"19","author":"Zhang","year":"2014","journal-title":"Nephrology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/jpp\/rgaa026","article-title":"Comparing the Pharmacokinetics of 13\u03b1,21-Dihydroeurycomanone and Eurycomanone Exclusively Enriched in Eurycoma Longifolia Extracts and Their Spermatogenesis Enhancement in Andrographolide-Induced Oligospermia in Rats","volume":"73","author":"Chung","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cai, W., Li, J., Chen, C., Wu, J., Li, J., and Xue, X. (2021). Design, Synthesis, and Anticancer Evaluation of Novel Andrographolide Derivatives Bearing an \u03b1,\u03b2-Unsaturated Ketone Moiety. Bioorg. Chem., 112.","DOI":"10.1016\/j.bioorg.2021.104941"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yang, T.C., Chiang, Y.J., Chiang, P.Y., Chen, H.Y., Zhuang, K.R., Wang, Y.C., Lin, C.H., Lo, L.C., and Fu, S.L. (2024). Design, Synthesis, and Anti-Cancer Evaluation of C-14 Arylcarbamate Derivatives of Andrographolide. Bioorg. Med. Chem., 98.","DOI":"10.1016\/j.bmc.2023.117582"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22510","DOI":"10.1039\/C5RA00090D","article-title":"SAR Studies of 3,14,19-Derivatives of Andrographolide on Anti-Proliferative Activity to Cancer Cells and Toxicity to Zebrafish: An in Vitro and in Vivo Study","volume":"5","author":"Peng","year":"2015","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1039\/C4MD00566J","article-title":"Synthesis and Evaluation of Anticancer Activity of Novel Andrographolide Derivatives","volume":"6","author":"Devendar","year":"2015","journal-title":"MedChemComm"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Messire, G., Rollin, P., Gillaizeau, I., and Berteina-Raboin, S. (2024). Synthetic Modifications of Andrographolide Targeting New Potential Anticancer Drug Candidates: A Comprehensive Overview. Molecules, 29.","DOI":"10.3390\/molecules29122884"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Satyanarayana, C., Deevi, D.S., Rajagopalan, R., Srinivas, N., and Rajagopal, S. (2004). DRF 3188 a Novel Semi-Synthetic Analog of Andrographolide: Cellular Response to MCF 7 Breast Cancer Cells. BMC Cancer, 4.","DOI":"10.1186\/1471-2407-4-26"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.1016\/j.bmcl.2004.06.090","article-title":"Synthesis and Structure-Activity Relationships of Andrographolide Analogues as Novel Cytotoxic Agents","volume":"14","author":"Nanduri","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.phytochem.2006.11.031","article-title":"Semisynthesis and in Vitro Anticancer Activities of Andrographolide Analogues","volume":"68","author":"Jada","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6099","DOI":"10.1021\/acsomega.3c00036","article-title":"Site-Selective Synthesis of C-17 Ester Derivatives of Natural Andrographolide for Evaluation as a Potential Anticancer Agent","volume":"8","author":"Kumar","year":"2023","journal-title":"ACS Omega"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5781","DOI":"10.1016\/j.bmcl.2015.10.053","article-title":"Synthesis and in Vitro Cytotoxicity of Novel C-12 Substituted-14-Deoxy-Andrographolide Derivatives as Potent Anti-Cancer Agents","volume":"25","author":"Kandanur","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1016\/j.bmcl.2017.04.033","article-title":"Synthesis and Biological Evaluation of New C-12(\u03b1\/\u03b2)-(N-) Sulfamoyl-Phenylamino-14-Deoxy-Andrographolide Derivatives as Potent Anti-Cancer Agents","volume":"27","author":"Kandanur","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5","article-title":"Click Chemistry: Diverse Chemical Function from a Few Good Reactions","volume":"40","author":"Kolb","year":"2001","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, S., Zhao, S., Wang, X., Liu, B., and Xu, H. (2021). Click Chemistry in Natural Product Modification. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.774977"},{"key":"ref_40","first-page":"1585","article-title":"The Application of Click Chemistry in the Synthesis of Agents with Anticancer Activity","volume":"9","author":"Ma","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.drudis.2017.07.007","article-title":"Mechanistic Applications of Click Chemistry for Pharmaceutical Drug Discovery and Drug Delivery","volume":"22","author":"Meghani","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_42","unstructured":"Meanwell, N.A., and Lolli, M.L. (2021). Chapter Three\u2014Click 1,2,3-Triazoles in Drug Discovery and Development: From the Flask to the Clinic?. Advances in Heterocyclic Chemistry, Academic Press."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.drudis.2017.05.014","article-title":"The 1,2,3-Triazole Ring as a Bioisostere in Medicinal Chemistry","volume":"22","author":"Bonandi","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ejmech.2017.01.044","article-title":"Dregamine and Tabernaemontanine Derivatives as ABCB1 Modulators on Resistant Cancer Cells","volume":"128","author":"Paterna","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112985","DOI":"10.1016\/j.ejmech.2020.112985","article-title":"Alkylated Monoterpene Indole Alkaloid Derivatives as Potent P-Glycoprotein Inhibitors in Resistant Cancer Cells","volume":"210","author":"Cardoso","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Cardoso, D.S.P., Szemer\u00e9di, N., Spengler, G., Mulhovo, S., Dos Santos, D.J.V.A., and Ferreira, M.J.U. (2021). Exploring the Monoterpene Indole Alkaloid Scaffold for Reversing P-Glycoprotein-Mediated Multidrug Resistance in Cancer. Pharmaceuticals, 14.","DOI":"10.3390\/ph14090862"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1111\/bph.15506","article-title":"BBIT20 Inhibits Homologous DNA Repair with Disruption of the BRCA1\u2013BARD1 Interaction in Breast and Ovarian Cancer","volume":"178","author":"Raimundo","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Reis, M.A., Matos, A.M., Duarte, N., Ahmed, O.B., Ferreira, R.J., Lage, H., and Ferreira, M.J.U. (2020). Epoxylathyrane Derivatives as MDR-Selective Compounds for Disabling Multidrug Resistance in Cancer. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00599"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1002\/cmdc.201600258","article-title":"Clickable 4-Oxo-b-Lactam-Based Selective Probing for Human Neutrophil Elastase Related Proteomes","volume":"11","author":"Ruivo","year":"2016","journal-title":"ChemMedChem"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1007\/s12272-013-0152-0","article-title":"12-Amino-Andrographolide Analogues: Synthesis and Cytotoxic Activity","volume":"36","author":"Kasemsuk","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1073\/pnas.94.7.2776","article-title":"The Cell Cycle and Cancer","volume":"94","author":"Collins","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-I","article-title":"A Novel Assay for Apoptosis. Flow Cytometric Detection of Phosphatidylserine Expression on Early Apoptotic Cells Using Fluorescein Labelled Annexin V","volume":"184","author":"Vermes","year":"1995","journal-title":"J. Immunol. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrm2312","article-title":"Apoptosis: Controlled Demolition at the Cellular Level","volume":"9","author":"Taylor","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_54","unstructured":"Nagai, T., and Honda, H. (2006, January 14\u201316). Wound Healing Mechanisms in Epithelial Tissues Cell Adhesion to Bsal Lamina. Proceedings of the 2006 WSEAS International Conference on Cellular & Molecular Biology, Biophyhsics & Bioengineering, Athens, Greece."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4161\/cam.36224","article-title":"Cell Adhesion & Migration An Introduction to the Wound Healing Assay Using Livecell Microscopy An Introduction to the Wound Healing Assay Using Livecell Microscopy","volume":"8","author":"Jonkman","year":"2014","journal-title":"Cell Adhes. Migr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1007\/s42250-023-00657-9","article-title":"Natural Andrographolide Isolated from Andrographis Paniculata as Potent Epileptic Agent: Spectroscopy, Molecular Structure, and Molecular Docking Investigation","volume":"6","author":"Owen","year":"2023","journal-title":"Chem. Afr."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Villedieu-Percheron, E., Ferreira, V., Campos, J.F., Destandau, E., Pichon, C., and Berteina-Raboin, S. (2019). Quantitative Determination of Andrographolide and Related Compounds in Andrographis Paniculata Extracts and Biological Evaluation of Their Anti-Inflammatory Activity. Foods, 8.","DOI":"10.3390\/foods8120683"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phrs.2015.03.006","article-title":"A Tryptophanol-Derived Oxazolopiperidone Lactam Is Cytotoxic against Tumors via Inhibition of P53 Interaction with Murine Double Minute Proteins","volume":"95\u201396","author":"Soares","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative Analysis of Dose-Effect Relationships: The Combined Effects of Multiple Drugs or Enzyme Inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzyme Regul."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3947","DOI":"10.1111\/bph.14468","article-title":"Improving Anticancer Activity towards Colon Cancer Cells with a New P53-Activating Agent","volume":"175","author":"Raimundo","year":"2018","journal-title":"Br. J. 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