Design, synthesis, and bioactivities of tasiamide B derivatives as cathepsin D inhibitors
Design, synthesis, and bioactivities of tasiamide B derivatives as cathepsin D inhibitors
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作为组织蛋白酶 D 抑制剂的 Tasiamide B 衍生物的设计、合成和生物活性
DOI：
10.1002/psc.3154
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发表时间：
2019-04
影响因子：
2.1
通讯作者：
Zhang Wei
中科院分区：
文献类型：
--
作者：
Li Zhi;Bao Keting;Xu Hao;Wu Ping;Li Wei;Liu Jian;Zhang Wei
组织蛋白酶D（Cathepsin D，Cath D）在恶性肿瘤中表达和分泌增加，参与肿瘤的侵袭、增殖、转移和凋亡。Cath D被认为是治疗癌症的潜在靶点。我们以前的研究表明，他磺酰胺B衍生物TB-9和TB-11对Cath D和其他天冬氨酸蛋白酶表现出高效的抑制作用，但它们的分子量仍然很高，并且每个残基的作用尚不清楚。在此基础上，设计、合成了两个系列的他磺酰胺B衍生物，并评价了它们对Cath D/Cath E/BACE 1的抑制活性。酶促活性测定结果表明，低分子量的目标化合物1对Cath D具有较好的抑制活性，IC 50为3.29 nM，对Cath E和BACE 1的选择性分别为72倍和295倍，可作为设计高效、高选择性Cath D抑制剂的有效模板。
Cathepsin D (Cath D) is overexpressed and hypersecreted by malignant tumors and involved in the progress of tumor invasion, proliferation, metastasis, and apoptosis. Cath D has been considered as a potential target to treat cancer. Our previous studies revealed that tasiamide B derivatives TB‐9 and TB‐11 exhibited high potent inhibition against Cath D and other aspartic proteases, but their molecular weights are still high, and the role of each residue is unknown yet. Based on this, two series of tasiamide B derivatives have been designed, synthesized, and evaluated for their inhibitory activity against Cath D/Cath E/BACE1. Enzymatic assays revealed that the target compound 1 with lower molecule weight showed good inhibitory activity against Cath D with IC50 of 3.29 nM and satisfactory selectivity over Cath E (72‐fold) and BACE1 (295‐fold), which could be a valuable template for the design of highly potent and selective Cath D inhibitors.
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影响因子：
2.7
作者：
Dumas, J;Brittelli, D;Wong, S
通讯作者：
Wong, S
影响因子：
1.3
作者：
Caroline Zhao;D. Herrington
通讯作者：
Caroline Zhao;D. Herrington
DOI：
10.1073/pnas.90.14.6796
发表时间：
1993-07-15
影响因子：
11.1
作者：
BALDWIN, ET;BHAT, TN;ERICKSON, JW
通讯作者：
ERICKSON, JW
影响因子：
0.8
作者：
Waseem Ahmed;I. Khan;M. Arshad;W. Siddiqui;M. A. Haleem;M. Azim
通讯作者：
Waseem Ahmed;I. Khan;M. Arshad;W. Siddiqui;M. A. Haleem;M. Azim
影响因子：
2.7
作者：
V. Srivastava;H. Saxena;K. Shanker;J. K. Kumar;Suaib Luqman;M. M. Gupta-M.;S. Khanuja;A. Negi
通讯作者：
V. Srivastava;H. Saxena;K. Shanker;J. K. Kumar;Suaib Luqman;M. M. Gupta-M.;S. Khanuja;A. Negi