Department of Polymer Science & Engineering, Chosun University, Gwangju, 501-759, South Korea.
Biotechnology Laboratory, B-K Company Ltd, Jeonbuk, 5703, Korea.
Arch Pharm Res. 2019 Sep;42(9):790-814. doi: 10.1007/s12272-018-1041-3. Epub 2018 Jun 8.
The aim of this work was to evaluate the synthesis and structure-activity relationship of 4-((2,4-dioxothiazolidin-5-ylidene)methyl)phenyl 2-phenylacetate derivatives as potential wound-healing agents. The IC values of the lead compounds ranged from 0.01 to 0.05 µM. These compounds also increased the levels of extracellular prostaglandin E (PGE) in A549 cells. Among the synthesized compounds, compounds 66, 67, 69, and 86 increased PGE levels 3- to 4-fold of those achieved with the negative control. Introduction of a halogen at the intermediate phenyl ring, compounds 66, 67, 69, and 86 resulted in higher IC values, which indicated lower cytotoxicity than that observed upon the introduction of other substituents at the same position. In particular, cells exposed to compound 69 showed significantly improved wound healing, and the wound closure rate achieved was approximately 3.2-fold higher than that of the control. Therefore, compound 69 can be used for tissue regeneration and treatment of diverse diseases caused by PGE deficiency. Overall, our findings suggested that compound 69 might be a novel candidate for skin wound therapy.
本工作旨在评估 4-((2,4-二氧代噻唑烷-5-亚基)甲基)苯基 2-苯乙酸酯衍生物作为潜在的伤口愈合剂的合成和构效关系。先导化合物的 IC 值范围为 0.01 至 0.05 µM。这些化合物还增加了 A549 细胞中细胞外前列腺素 E(PGE)的水平。在合成的化合物中，化合物 66、67、69 和 86 将 PGE 水平提高到阴性对照的 3 至 4 倍。在中间苯基环上引入卤素，化合物 66、67、69 和 86 的 IC 值更高，表明其细胞毒性低于在同一位置引入其他取代基时观察到的细胞毒性。特别是，暴露于化合物 69 的细胞显示出明显改善的伤口愈合，并且达到的伤口闭合率比对照高约 3.2 倍。因此，化合物 69 可用于组织再生和治疗由 PGE 缺乏引起的各种疾病。总体而言，我们的研究结果表明，化合物 69 可能是一种新型的皮肤伤口治疗候选药物。
