HE Qin,ZHANG Huan,DU Xuze, et al. The design, synthesis and biological activity of small molecule inhibitors targeting STAT3 signaling pathway[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(5): 333-338,343.
Abstract：Objective: Based on the lead compound, STAT3 small molecule inhibitor S3I-V4-01, a series of novel target compounds were designed and synthesized and their biological activity were tested by preliminary in vitro cell experiments so as to screen the more potent compounds. Methods: A series of target compounds were synthesized by nucleophilic substitution reaction; Luciferase reporter gene assay was used to measure the effect of target compounds on STAT3 signal transduction pathway; MTT assay was used to detect the inhibitory effect of target compounds on proliferation of human epidermal squamous cell carcinoma A431 and non-small cell lung cancer cell lines A549 cells. Results: In this study, eight target compounds (Z2-Z5 and H2-H5) were synthesized. Among them, the dominant compound H3 could effectively inhibit the phosphorylation of STAT3 and block the STAT3 signal transduction pathway and inhibit the proliferation of A431 and A549 cells. Conclusion: Compound H3 had stronger p-STAT3 inhibition and anti-proliferation ability than S3I-V4-01, and it could also be optimized in H3 structure to further improve biological activity.
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