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Synthesis, Structural Analysis, and Biological Evaluation of Novel ((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl Derivatives
Biotechnology and Bioprocess Engineering ( IF 3.2 ) Pub Date : 2020-04-29 , DOI: 10.1007/s12257-019-0308-y
A Ri Na , Dubok Choi , Hoon Cho

The objective of this study was to evaluate the synthesis, structural analysis, and biological effects of novel ((2, 4-dioxothiazolidin-5-ylidene)methyl)phenyl derivatives. The efficacy of 15-PGDH inhibition increased for the substituents in the derivatives in the order: cyclohexylpropyl > cyclohexylethyl > cyclohexylmethyl > cyclohexyl. Compound 12 inhibited 15-PGDH activity by binding to the amino acids Ile 214, Ile 210, Ile 194, Gln 148, and Leu 191 of 15-PGDH. Compounds 4, 22, and 23 produced the highest increment in PGE2 concentration, which was 122.19, 100.14, and 206.80%, respectively, compared to that of the control. Also, compounds 38 and 39, in which the central phenyl ring and the 2, 4-thiazolidinedione moiety were linked by a single bond, produced a relatively high increment in PGE2 concentration, which was 106.81 and 118.66%, respectively, compared to that of the control. The wound closure rates of compounds 22 and 39 were the highest, being 247.56 and 202.42%, respectively, compared to that of the positive control. Therefore, compounds 22 and 39 could not only efficiently regulate PGE2 concentration, but also induce cellular regeneration, and are expected to effectively treat a variety of diseases resulting from PGE2 deficiency.



中文翻译:

新型((2,4-二氧噻唑啉--5-亚甲基)甲基)苯基衍生物的合成,结构分析和生物评价

这项研究的目的是评估新型((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl衍生物的合成,结构分析和生物学效应。对于衍生物中的取代基,抑制15-PGDH的功效按以下顺序增加:环己基丙基>环己基乙基>环己基甲基>环己基。化合物12通过与15-PGDH的氨基酸Ile 214,Ile 210,Ile 194,Gln 148和Leu 191结合而抑制15-PGDH活性。化合物4,2223所产生的PGE最高增量2浓度,其分别为122.19,100.14,206.80和%,相对于对照的。另外,化合物3839,其中中央苯环和2,4-噻唑烷二酮部分通过单键连接,与对照相比,PGE 2的浓度相对较高,分别为106.81和118.66%。与阳性对照相比,化合物2239的伤口闭合率最高,分别为247.56和202.42%。因此,化合物2239不仅可以有效地调节PGE 2的浓度,而且还可以诱导细胞再生,并有望有效治疗由于PGE 2缺乏引起的多种疾病。

更新日期:2020-04-29
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