{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:18:53Z","timestamp":1788221933594,"version":"build-2803163510"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Isra University","award":["51\/3-2018\/2019"],"award-info":[{"award-number":["51\/3-2018\/2019"]}]},{"name":"Isra University","award":["2023-2022\/17\/50"],"award-info":[{"award-number":["2023-2022\/17\/50"]}]},{"name":"Deanship of Scientific Research at Al-Zaytoonah University of Jordan for the computational resources and databases","award":["51\/3-2018\/2019"],"award-info":[{"award-number":["51\/3-2018\/2019"]}]},{"name":"Deanship of Scientific Research at Al-Zaytoonah University of Jordan for the computational resources and databases","award":["2023-2022\/17\/50"],"award-info":[{"award-number":["2023-2022\/17\/50"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Carboxamide derivatives are a promising class of compounds in anticancer drug discovery, owing to their ability to interact with multiple oncogenic targets and their favorable pharmacological profiles. In this study, we report the design, synthesis, and biological evaluation of a series of N-substituted 1H-indole-2-carboxamides as potential anticancer agents. The synthesized compounds were assessed for antiproliferative activity using the MTT assay against MCF-7 (breast cancer), K-562 (leukemia), and HCT-116 (colon cancer) cell lines, with normal human dermal fibroblasts included as a non-cancerous control. Several compounds demonstrated notable cytotoxicity and selectivity. Compounds 12, 14, and 4 exhibited potent activity against K-562 cells, with IC50 values of 0.33 \u00b5M, 0.61 \u00b5M, and 0.61 \u00b5M, respectively. Compound 10 showed the most significant activity against HCT-116 cells (IC50 = 1.01 \u00b5M) with a high selectivity index (SI = 99.4). Moderate cytotoxicity was observed against MCF-7 cells. To elucidate the mechanism of action, molecular docking and induced-fit docking studies were conducted against key cancer-related targets, including topoisomerase\u2013DNA (PDB ID: 5ZRF), PI3K\u03b1 (4L23), and EGFR (3W32), revealing favorable binding interactions. Additionally, principal component analysis of molecular descriptors indicated that the compounds possess promising drug-like and lead-like properties, particularly compound 10. Overall, this study highlights N-substituted indole-2-carboxamides as promising scaffolds for further optimization. The integration of synthetic chemistry, biological assays, and computational modeling provides a robust foundation for the continued development of these compounds as potential anticancer agents.<\/jats:p>","DOI":"10.3390\/ijms26125903","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T08:43:58Z","timestamp":1750322638000},"page":"5903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Exploring Carboxamide Derivatives as Promising Anticancer Agents: Design, In Vitro Evaluation, and Mechanistic Insights"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4372-997X","authenticated-orcid":false,"given":"Manal M.","family":"Al-Najdawi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetics, Faculty of Pharmacy Middle East University, Amman 11831, Jordan"},{"name":"Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3140-4038","authenticated-orcid":false,"given":"Maysaa M.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-5097","authenticated-orcid":false,"given":"Dima A.","family":"Sabbah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-5425","authenticated-orcid":false,"given":"Rima","family":"Hajjo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan"},{"name":"Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC 27599, USA"},{"name":"Advisory Board, Jordan CDC, Amman 11118, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-2776","authenticated-orcid":false,"given":"Hiba","family":"Zalloum","sequence":"additional","affiliation":[{"name":"Hamdi Mango Center for Scientific Research, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7934-8250","authenticated-orcid":false,"given":"Suha M.","family":"Abudoleh","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Middle East University, Amman 11831, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5277-5703","authenticated-orcid":false,"given":"Duaa A.","family":"Abuarqoub","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan"},{"name":"Cell Therapy Center, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4416-9193","authenticated-orcid":false,"given":"Yusuf M.","family":"Al-Hiari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0641-1586","authenticated-orcid":false,"given":"Mohammad Yasin","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-7491","authenticated-orcid":false,"given":"Husam","family":"ALSalamat","sequence":"additional","affiliation":[{"name":"Hamdi Mango Center for Scientific Research, The University of Jordan, Amman 11942, Jordan"},{"name":"Department of Pharmacology, School of Medicine, Al-Balqa Applied University, Al-Salt 19117, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1202-7830","authenticated-orcid":false,"given":"Hebah","family":"Mansour","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Isra University, Amman 11622, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5714-3753","authenticated-orcid":false,"given":"Nawzat D.","family":"Aljbour","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetics, Faculty of Pharmacy Middle East University, Amman 11831, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-6310","authenticated-orcid":false,"given":"Aktham H.","family":"Mestareehi","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan"},{"name":"Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e39402","DOI":"10.1016\/j.heliyon.2024.e39402","article-title":"Downregulation of aquaporins and PI3K\/AKT and upregulation of PTEN expression induced by the flavone scutellarein in human colon cancer cell lines","volume":"10","author":"Tarawneh","year":"2024","journal-title":"Heliyon"},{"key":"ref_4","unstructured":"(2023, September 14). Cancer Facts & Figures. Available online: https:\/\/www.cancer.org\/content\/dam\/cancer-org\/research\/cancer-facts-and-statistics\/annual-cancer-facts-and-figures\/2021\/cancer-facts-and-figures-2021.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1021\/acsabm.4c00479","article-title":"A Glucose Oxidase-Curcumin Composite Nanoreactor for Multimodal Synergistic Cancer Therapy","volume":"7","author":"Alsamarat","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9979234","DOI":"10.1155\/2021\/9979234","article-title":"Metformin Increases Protein Phosphatase 2A Activity in Primary Human Skeletal Muscle Cells Derived from Lean Healthy Participants","volume":"2021","author":"Mestareehi","year":"2021","journal-title":"J. Diabetes Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12964-023-01302-1","article-title":"Unveiling the mechanisms and challenges of cancer drug resistance","volume":"22","author":"Khan","year":"2024","journal-title":"J. Cell Commun. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1016\/j.cellsig.2007.05.013","article-title":"Vascular endothelial growth factor receptor-2: Structure, function, intracellular signalling and therapeutic inhibition","volume":"19","author":"Holmes","year":"2007","journal-title":"Cell. Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10299","DOI":"10.1021\/acsomega.3c07787","article-title":"Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients","volume":"9","author":"Mestareehi","year":"2024","journal-title":"ACS Omega"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4062\/biomolther.2013.113","article-title":"VEGF-VEGFR Signals in Health and Disease","volume":"22","author":"Shibuya","year":"2014","journal-title":"Biomol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13045-022-01310-7","article-title":"Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy","volume":"15","author":"Liu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10144","article-title":"Molecular mechanisms and clinical applications of angiogenesis","volume":"473","author":"Carmeliet","year":"2011","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrd.2015.17","article-title":"Ten years of anti-vascular endothelial growth factor therapy","volume":"15","author":"Ferrara","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3322\/caac.21411","article-title":"Treatment of renal cell carcinoma: Current status and future directions","volume":"67","author":"Barata","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26075","DOI":"10.1021\/acsomega.4c01496","article-title":"Global Gene Expression Profiling and Bioinformatics Analysis Reveal Downregulated Biomarkers as Potential Indicators for Hepatocellular Carcinoma","volume":"9","author":"Mestareehi","year":"2024","journal-title":"ACS Omega"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1158\/1078-0432.CCR-22-1366","article-title":"Molecular Mechanisms and Future Implications of VEGF\/VEGFR in Cancer Therapy","volume":"29","author":"Patel","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.chembiol.2010.04.012","article-title":"DNA topoisomerases and their poisoning by anticancer and antibacterial drugs","volume":"17","author":"Pommier","year":"2010","journal-title":"Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/S0959-8049(98)00228-7","article-title":"Etoposide: Four decades of development of a topoisomerase II inhibitor","volume":"34","author":"Hande","year":"1998","journal-title":"Eur. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mestareehi, A.H. (2025). Optimized and Validated Stability-Indicating RP-HPLC Method for Comprehensive Profiling of Process-Related Impurities and Stress-Induced Degradation Products in Rivaroxaban (XARELTO)(\u00ae). Int. J. Mol. Sci., 26.","DOI":"10.2139\/ssrn.5229223"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.2174\/092986710793361252","article-title":"Recent advances in the development of dual topoisomerase I and II inhibitors as anticancer drugs","volume":"17","author":"Salerno","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev.pa.34.040194.001203","article-title":"DNA topoisomerases: Essential enzymes and lethal targets","volume":"34","author":"Chen","year":"1994","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mestareehi, A. (2025). Development and validation of a stability-indicating reversed phase high-performance liquid chromatography method for quantifying rivaroxaban (XARELTO). J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 1257.","DOI":"10.1016\/j.jchromb.2025.124573"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00044-015-1495-5","article-title":"Development of drugs based on imidazole and benzimidazole bioactive heterocycles: Recent advances and future directions","volume":"25","author":"Gaba","year":"2016","journal-title":"Med. Chem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1021\/cn5000056","article-title":"Classics in chemical neuroscience: Diazepam (valium)","volume":"5","author":"Calcaterra","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dhuguru, J., and Skouta, R. (2020). Role of Indole Scaffolds as Pharmacophores in the Development of Anti-Lung Cancer Agents. Molecules, 25.","DOI":"10.3390\/molecules25071615"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1134\/S1068162023060018","article-title":"A Perspective of the Amide Group Containing FDA Approved Anticancer Drugs from 2021\u20132022 (A Review)","volume":"49","author":"Asif","year":"2023","journal-title":"Russ. J. Bioorganic Chem."},{"key":"ref_27","first-page":"3147","article-title":"The Story of MCF-7 Breast Cancer Cell Line: 40 years of Experience in Research","volume":"35","author":"Raica","year":"2015","journal-title":"Anticancer. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12361","DOI":"10.1021\/acsomega.1c01604","article-title":"Design, Synthesis, Anticancer Evaluation, Enzymatic Assays, and a Molecular Modeling Study of Novel Pyrazole-Indole Hybrids","volume":"6","author":"Hassan","year":"2021","journal-title":"ACS Omega"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s12079-017-0412-8","article-title":"K562 chronic myeloid leukemia cells modify osteogenic differentiation and gene expression of bone marrow stromal cells","volume":"12","author":"Kumar","year":"2018","journal-title":"J. Cell Commun. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rubin, E., Shan, K.S., Dalal, S., Vu, D.U.D., Milillo-Naraine, A.M., Guaqueta, D., and Ergle, A. (2024). Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021064"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Miziak, P., Baran, M., B\u0142aszczak, E., Przybyszewska-Podstawka, A., Ka\u0142afut, J., Smok-Kalwat, J., Dmoszy\u0144ska-Graniczka, M., Kie\u0142bus, M., and Stepulak, A. (2023). Estrogen Receptor Signaling in Breast Cancer. Cancers, 15.","DOI":"10.3390\/cancers15194689"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Li, L., Liu, S., Wang, B., Liu, F., Xu, S., Li, P., and Chen, Y. (2023). An Updated Review on Developing Small Molecule Kinase Inhibitors Using Computer-Aided Drug Design Approaches. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.2046.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16206","DOI":"10.1021\/acsomega.3c00678","article-title":"Quantitative Proteomics Reveals Transforming Growth Factor \u03b2 Receptor Targeted by Resveratrol and Hesperetin Coformulation in Endothelial Cells","volume":"8","author":"Mestareehi","year":"2023","journal-title":"ACS Omega"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0022-1759(86)90368-6","article-title":"Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability","volume":"89","author":"Denizot","year":"1986","journal-title":"J. Immunol. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1038\/s41467-018-05406-y","article-title":"Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1021\/ml400378e","article-title":"Crystal structures of PI3Kalpha complexed with PI103 and Its derivatives: New directions for inhibitors design","volume":"5","author":"Zhao","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1016\/j.bmc.2013.02.014","article-title":"Design and synthesis of novel pyrimido [4,5-b]azepine derivatives as HER2\/EGFR dual inhibitors","volume":"21","author":"Kawakita","year":"2013","journal-title":"Bioorganic Med. Chem."},{"key":"ref_39","unstructured":"Schr\u00f6dinger (2022). Protein Preparation Wizard, Maestro, Macromodel, QPLD-Dock, and Pymol, Schr\u00f6dinger, LLC."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s40203-017-0024-2","article-title":"Molecular docking studies on thirteen fluoroquinolines with human topoisomerase II a and b","volume":"5","author":"Jadhav","year":"2016","journal-title":"Silico Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"176","DOI":"10.2174\/1573409915666190820144759","article-title":"Molecular Docking Based Analysis to Elucidate the DNA Topoisomerase II\u03b2 as the Potential Target for the Ganoderic Acid; A Natural Therapeutic Agent in Cancer Therapy","volume":"16","author":"Sharma","year":"2020","journal-title":"Curr. Comput.-Aided Drug Des."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/cbdd.13927","article-title":"Identification of novel topoisomerase II alpha inhibitors by virtual screening, molecular docking, and bioassay","volume":"99","author":"Yu","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jrid.2019.06.003","article-title":"Molecular docking studies of some topoisomerase II inhibitors: Implications in designing of novel anticancer drugs","volume":"6","author":"Arthur","year":"2019","journal-title":"Radiol. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e202200662","DOI":"10.1002\/slct.202200662","article-title":"Design, Synthesis, and Biological Examination of N-Phenyl-6-fluoro-4-hydroxy-2-quinolone-3-carboxamides as Anticancer Agents","volume":"7","author":"Sabbah","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e202202263","DOI":"10.1002\/slct.202202263","article-title":"Novel Derivatives of 4,6-Dihydroxy-2-Quinolone-3-Carboxamides as Potential PI3K\u03b1 Inhibitors","volume":"7","author":"Sweidan","year":"2022","journal-title":"ChemistrySelect"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"856","DOI":"10.2174\/1570180812666150529205248","article-title":"Computational docking studies of novel heterocyclic carboxamides as potential PI3K\u03b1 inhibitors","volume":"12","author":"Sweidan","year":"2015","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1139\/cjc-2018-0145","article-title":"Synthesis, characterization, and anticancer evaluation of some new N1-(anthraquinon-2-yl) amidrazone derivatives","volume":"96","author":"Sweidan","year":"2018","journal-title":"Can. J. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1016\/j.bmcl.2016.04.011","article-title":"Computer-aided design, synthesis, and biological evaluation of new indole-2-carboxamide derivatives as PI3K\u03b1\/EGFR inhibitors","volume":"26","author":"Sweidan","year":"2016","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2174\/1573406414666180912111846","article-title":"Ligand-based drug design: Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents","volume":"15","author":"Sabbah","year":"2019","journal-title":"Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sabbah, D.A., Hasan, S.E., Abu Khalaf, R., Bardaweel, S.K., Hajjo, R., Alqaisi, K.M., Sweidan, K.A., and Al-Zuheiri, A.M. (2020). Molecular modeling, synthesis and biological evaluation of N-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamides as anticancer agents. Molecules, 25.","DOI":"10.3390\/molecules25225348"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sabbah, D.A., Haroon, R.A., Bardaweel, S.K., Hajjo, R., and Sweidan, K. (2021). N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents. Molecules, 26.","DOI":"10.3390\/molecules26010073"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"695","DOI":"10.2174\/1573406414666180412160142","article-title":"Benzoin schiff bases: Design, synthesis, and biological evaluation as potential antitumor agents","volume":"14","author":"Sabbah","year":"2018","journal-title":"Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1021\/ci3003057","article-title":"Binding selectivity studies of phosphoinositide 3-kinases using free energy calculations","volume":"52","author":"Sabbah","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1021\/ci1002679","article-title":"Docking studies on isoform-specific inhibition of phosphoinositide-3-kinases","volume":"50","author":"Sabbah","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7175","DOI":"10.1016\/j.bmc.2012.09.059","article-title":"N-Phenyl-4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R phosphoinositide-3-kinase (PI3K\u03b1)","volume":"20","author":"Sabbah","year":"2012","journal-title":"Bioorganic Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.bmcl.2011.12.044","article-title":"Biological evaluation and docking studies of recently identified inhibitors of phosphoinositide-3-kinases","volume":"22","author":"Sabbah","year":"2012","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1016\/j.bmcl.2015.06.011","article-title":"Molecular modeling based approach, synthesis, and cytotoxic activity of novel benzoin derivatives targeting phosphoinostide 3-kinase (PI3K\u03b1)","volume":"25","author":"Sabbah","year":"2015","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"263","DOI":"10.2174\/1871520617666170911171152","article-title":"Structure-based design: Synthesis, X-ray crystallography, and biological evaluation of N-substituted-4-hydroxy-2-quinolone-3-carboxamides as potential cytotoxic agents","volume":"18","author":"Sabbah","year":"2018","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1126\/science.1150799","article-title":"The structure of a human p110 alpha\/p85 alpha complex elucidates the effects of oncogenic PI3K alpha mutations","volume":"318","author":"Huang","year":"2007","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/157340611794072698","article-title":"Docking and molecular dynamics study on the inhibitory activity of novel inhibitors on epidermal growth factor receptor (EGFR)","volume":"7","author":"Liao","year":"2011","journal-title":"Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.ejmech.2019.04.012","article-title":"Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors","volume":"173","author":"Celik","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"112640","DOI":"10.1016\/j.ejmech.2020.112640","article-title":"Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015\u20132019)","volume":"204","author":"Bhatia","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_66","unstructured":"(2023, October 10). alvaDesc 2.0. Available online: http:\/\/dev.kode-datacenter.net:10050\/pf\/alvadesc-2-0\/."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.1016\/j.bmcl.2006.08.003","article-title":"Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis","volume":"16","author":"Hopkins","year":"2006","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5560\/znc.2012-0224","article-title":"Synthesis and pharmacological evaluation of novel unsubstituted indole-anthraquinone carboxamide derivatives as potent antihyperlipidemic agents","volume":"69","author":"Shattat","year":"2014","journal-title":"Z. Naturforsch. C"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3390\/cimb45010014","article-title":"In Vitro Anticancer Properties of Novel Bis-Triazoles","volume":"45","author":"Saleh","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e187410452207200","DOI":"10.2174\/18741045-v16-e2207200","article-title":"Biological Evaluation and Reverse Pharmacophore Mapping of Innovative Bis-Triazoles as Promising Anticancer Agents","volume":"16","author":"Saleh","year":"2022","journal-title":"Open J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"47297","DOI":"10.1039\/C7RA07257K","article-title":"Development of a series of bis-triazoles as G-quadruplex ligands","volume":"7","author":"Saleh","year":"2017","journal-title":"RSC Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"909","DOI":"10.18596\/jotcsa.1092553","article-title":"Synthesis and Biological Evaluation of Furyl-Carboxamide Derivatives as Potential Anticancer Agents","volume":"9","author":"Saleh","year":"2022","journal-title":"J. Turk. Chem. Soc. A Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"101931","DOI":"10.1016\/j.jsps.2023.101931","article-title":"Biological evaluation of combinations of tyrosine kinase inhibitors with Inecalcitol as novel treatments for human chronic myeloid leukemia","volume":"32","author":"Saleh","year":"2024","journal-title":"Saudi Pharm. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.31557\/APJCP.2022.23.10.3533","article-title":"Anti-Proliferative Effect of Potential LSD1\/CoREST Inhibitors Based on Molecular Dynamics Model for Treatment of SH-SY5Y Neuroblastoma Cancer Cell Line","volume":"23","author":"Zalloum","year":"2022","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8388","DOI":"10.1021\/ja204075s","article-title":"Computer review of ChemDraw Ultra 12.0","volume":"133","author":"Cousins","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7573","DOI":"10.1021\/jm100600y","article-title":"Development, validation, and use of quantitative structure-activity relationship models of 5-hydroxytryptamine (2B) receptor ligands to identify novel receptor binders and putative valvulopathic compounds among common drugs","volume":"53","author":"Hajjo","year":"2010","journal-title":"J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5903\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:55:06Z","timestamp":1760032506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":76,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125903"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125903","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]}}}