{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:25:37Z","timestamp":1788272737823,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek","award":["IP-11-2021"],"award-info":[{"award-number":["IP-11-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d, 8d, and 12d, showed strong cytotoxic activity (the GI50 ranged from 0.4 to 8 \u00b5M) and effectively suppressed the cell cycle progression in the leukemia and lymphoma cells. After 24 h of treatment, compounds 5d and 12d induced the disruption of the mitochondrial membrane potential as well as apoptosis in HuT78 cells. The drug-like properties and bioavailability of the compounds were calculated using the Swiss ADME web tool, and a molecular docking study was performed on tyrosine-protein kinase c-Src (PDB: 3G6H). Compound 12d showed good solubility and permeability and bound to c-Src with an energy of \u2212119.99 kcal\/mol, forming hydrogen bonds with Glu310 and Asp404 in the active site and other residues with van der Waals interactions. The results suggest that compound 12d could be a leading compound in the further design of effective antitumor drugs.<\/jats:p>","DOI":"10.3390\/molecules28020540","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T02:20:30Z","timestamp":1672971630000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking"],"prefix":"10.3390","volume":"28","author":[{"given":"Luka","family":"Krstulovi\u0107","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijana","family":"Leventi\u0107","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-4022","authenticated-orcid":false,"given":"Vesna","family":"Rastija","sequence":"additional","affiliation":[{"name":"Department of Agroecology and Environmental Protection, Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-7807","authenticated-orcid":false,"given":"Kristina","family":"Star\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Jirou\u0161","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Jani\u0107","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-0012","authenticated-orcid":false,"given":"Maja","family":"Karna\u0161","sequence":"additional","affiliation":[{"name":"Department of Agroecology and Environmental Protection, Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kornelija","family":"Lasi\u0107","sequence":"additional","affiliation":[{"name":"R&D, Pliva Croatia Ltd., TEVA Group Member, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Baji\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Veterinary Medicine, University of Zagreb, HR-10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-296X","authenticated-orcid":false,"given":"Ljubica","family":"Glava\u0161-Obrovac","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"ref_1","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":"2021","journal-title":"CA A Cancer J. 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