新型吡唑基噻唑烷酮/噻唑衍生物作为塞来昔布/达沙替尼类似物，具有选择性 COX-2、HER-2 和 EGFR 抑制作用：设计、合成、抗炎/抗增殖活性、细胞凋亡、分子模拟和 ADME 研究。
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.
机构信息
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Immunology Division, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
出版信息
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2281262. doi: 10.1080/14756366.2023.2281262. Epub 2023 Nov 27.
Two new series of pyrazolyl-thiazolidinone/thiazole derivatives and were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds , and inhibit with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds and inhibit with IC = 0.73-6.25 μM (dasatinib IC = 7.99 μM) and (doxorubicin IC50 = 3.1 μM) and inhibit with IC50 = 1.64-14.3 μM (dasatinib IC = 11.8 μM and doxorubicin IC = 2.42 μM) with S.I. 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. 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 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.
合成了两个新的吡唑基噻唑烷酮/噻唑衍生物系列 和 ，将塞来昔布和达沙替尼的骨架融合在一起。化合物 、 和 对 的抑制作用分别为 S.I. 134.6、26.08 和 42.13（塞来昔布 S.I. = 24.09）。化合物 、 和 对 的抑制作用分别为 IC = 0.73-6.25 μM（达沙替尼 IC = 7.99 μM）和（阿霉素 IC50 = 3.1 μM）和抑制作用为 IC50 = 1.64-14.3 μM（达沙替尼 IC = 11.8 μM 和阿霉素 IC = 2.42 μM），S.I. 分别为 33.15、7.13、18.72、13.25 和 8.28，均高于达沙替尼（4.03）和阿霉素（3.02），S.I. 分别为 14.75、12.96、4.16、7.07 和 18.88，均高于达沙替尼（S.I. = 2.72）和阿霉素（S.I = 3.88）。衍生物 对 EGFR 和 HER-2 的抑制作用分别为 EGFR 的 IC50 为 0.043、0.226、0.388、0.19 μM，HER-2 的 IC50 为 0.032、0.144、0.195、0.201 μM。
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