{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:28:14Z","timestamp":1774499294791,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Academy of Sciences of Belarus","award":["2.3.2"],"award-info":[{"award-number":["2.3.2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>In this work, fragments of isophthalic and terephthalic acids are proposed as a structural scaffold to develop potential inhibitors of protein kinases. Novel isophthalic and terephthalic acid derivatives were designed as type-2 protein kinase inhibitors, synthesized and subjected to physicochemical characterization. The screening of their cytotoxic actions against a panel of cell lines derived from different types of tumors (liver, renal, breast and lung carcinomas, as well as chronic myelogenous and promyelocytic leukemia) and normal human B lymphocyte, for the sake of comparison, was performed. Compound 5 showed the highest inhibitory activity against four cancer cell lines, K562, HL-60, MCF-7 and HepG2 (IC50 = 3.42, 7.04, 4.91 and 8.84 \u00b5M, respectively). Isophthalic derivative 9 revealed a high potency against EGFR and HER2, at the levels of 90% and 64%, respectively, being comparable to lapatinib at 10 \u00b5M. In general, tumor cell cultures were more sensitive to isophthalic acid derivatives than to terephthalic acid ones. In cell cycle studies, isophthalic analogue 5 showed a pronounced dose-dependent effect, and with the increase in its concentration up to 10.0 \u00b5M, the number of living cells decreased to 38.66%, while necrosis reached 16.38%. The considered isophthalic compounds had a similar docking performance to that of sorafenib against the VEGFR-2 (PDB id: 4asd, 3wze). The correct binding of compounds 11 and 14 with VEGFR-2 was validated using MD simulations and MM-GPSA calculations.<\/jats:p>","DOI":"10.3390\/cimb45030117","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T03:56:58Z","timestamp":1677124618000},"page":"1820-1842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel Phthalic-Based Anticancer Tyrosine Kinase Inhibitors: Design, Synthesis and Biological Activity"],"prefix":"10.3390","volume":"45","author":[{"given":"Elena","family":"Kalinichenko","sequence":"first","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 5\/2 Academician V.F. Kuprevich Street, BY-220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliaksandr","family":"Faryna","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 5\/2 Academician V.F. Kuprevich Street, BY-220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Bozhok","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 5\/2 Academician V.F. Kuprevich Street, BY-220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Golyakovich","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 5\/2 Academician V.F. Kuprevich Street, BY-220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alesya","family":"Panibrat","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 5\/2 Academician V.F. Kuprevich Street, BY-220141 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2165\/00003495-200767020-00010","article-title":"Imatinib: A review of its use in chronic myeloid leukaemia","volume":"67","author":"Moen","year":"2007","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"942500","DOI":"10.3389\/fcell.2022.942500","article-title":"Recent advances in targeting protein kinases and pseudokinases in cancer biology","volume":"10","author":"Riegel","year":"2022","journal-title":"Front. Cell Dev. 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