Wael A A Fadaly, Taha H Zidan, Nesma M Kahk, Fatma E A Mohamed, Marwa M Abdelhakeem, Rehab G Khalil, Mohamed T M Nemr
{"title":"具有选择性COX-2、HER-2和EGFR抑制作用的新型吡唑基噻唑烷酮/噻唑衍生物塞来昔布/达沙替尼类似物:设计、合成、抗炎/抗增殖活性、细胞凋亡、分子模型和ADME研究","authors":"Wael A A Fadaly, Taha H Zidan, Nesma M Kahk, Fatma E A Mohamed, Marwa M Abdelhakeem, Rehab G Khalil, Mohamed T M Nemr","doi":"10.1080/14756366.2023.2281262","DOIUrl":null,"url":null,"abstract":"<p><p>Two new series of pyrazolyl-thiazolidinone/thiazole derivatives <b>16a-b</b> and <b>18a-j</b> were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds <b>16a</b>, <b>16b</b> and <b>18f</b> inhibit <b>COX-2</b> with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds <b>16a,</b> <b>16b,</b> <b>18c,</b> <b>18d</b> and <b>18f</b> inhibit <b>MCF-7</b> with IC<sub>50</sub> = 0.73-6.25 μM (dasatinib IC<sub>50</sub> = 7.99 μM) and (doxorubicin IC50 = 3.1 μM) and inhibit <b>A549</b> with IC50 = 1.64-14.3 μM (dasatinib IC<sub>50</sub> = 11.8 μM and doxorubicin IC<sub>50</sub> = 2.42 μM) with S.I. <b>(F180/MCF7)</b> of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. <b>(F180/A549)</b> of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives <b>16a, 18c, 18d, 18f</b> inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 μM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 μM respectively.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003491/pdf/","citationCount":"0","resultStr":"{\"title\":\"New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies.\",\"authors\":\"Wael A A Fadaly, Taha H Zidan, Nesma M Kahk, Fatma E A Mohamed, Marwa M Abdelhakeem, Rehab G Khalil, Mohamed T M Nemr\",\"doi\":\"10.1080/14756366.2023.2281262\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Two new series of pyrazolyl-thiazolidinone/thiazole derivatives <b>16a-b</b> and <b>18a-j</b> were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds <b>16a</b>, <b>16b</b> and <b>18f</b> inhibit <b>COX-2</b> with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds <b>16a,</b> <b>16b,</b> <b>18c,</b> <b>18d</b> and <b>18f</b> inhibit <b>MCF-7</b> with IC<sub>50</sub> = 0.73-6.25 μM (dasatinib IC<sub>50</sub> = 7.99 μM) and (doxorubicin IC50 = 3.1 μM) and inhibit <b>A549</b> with IC50 = 1.64-14.3 μM (dasatinib IC<sub>50</sub> = 11.8 μM and doxorubicin IC<sub>50</sub> = 2.42 μM) with S.I. <b>(F180/MCF7)</b> of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. <b>(F180/A549)</b> of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives <b>16a, 18c, 18d, 18f</b> inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 μM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 μM respectively.</p>\",\"PeriodicalId\":15769,\"journal\":{\"name\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003491/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14756366.2023.2281262\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Enzyme Inhibition and Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14756366.2023.2281262","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies.
Two new series of pyrazolyl-thiazolidinone/thiazole derivatives 16a-b and 18a-j were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds 16a, 16b and 18f inhibit COX-2 with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds 16a,16b,18c,18d and 18f inhibit MCF-7 with IC50 = 0.73-6.25 μM (dasatinib IC50 = 7.99 μM) and (doxorubicin IC50 = 3.1 μM) and inhibit A549 with IC50 = 1.64-14.3 μM (dasatinib IC50 = 11.8 μM and doxorubicin IC50 = 2.42 μM) with S.I. (F180/MCF7) of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. (F180/A549) of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives 16a, 18c, 18d, 18f inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 μM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 μM respectively.
期刊介绍：
Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents.
Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research.
The journal’s focus includes current developments in:
Enzymology;
Cell biology;
Chemical biology;
Microbiology;
Physiology;
Pharmacology leading to drug design;
Molecular recognition processes;
Distribution and metabolism of biologically active compounds.
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