Abstract：
STAT3 is a crucial member within a family of seven essential transcription factors. Elevated STAT3 levels have been identified in various cancer types, notably in breast cancer (BC). Consequently, inhibiting STAT3 is recognized as a promising and effective strategy for therapeutic intervention against breast cancer. We herein synthesize a library of isoxazole (PAIs) from piperic acid [2E, 4E)-5-(2H-1,3-Benzodioxol-5-yl) penta-2,4-dienoic acid] on treatment with propargyl bromide followed by oxime under prescribed reaction conditions. Piperic acid was obtained by hydrolysis of piperine extracted from Piper nigrum. First, we checked the binding potential of isoxazole derivatives with breast cancer target proteins by network pharmacology, molecular docking, molecular dynamic (MD) simulation and cytotoxicity analysis as potential anti-breast cancer (BC) agents. The multi-source databases were used to identify possible targets for isoxazole derivatives. A network of protein-protein interactions (PPIs) was generated by obtaining 877 target genes that overlapped gene symbols associated with isoxazole derivatives and BC. Molecular docking and MD modelling demonstrated a strong affinity between isoxazole derivatives and essential target genes. Further, the cell viability studies of isoxazole derivatives on the human breast carcinoma cell lines showed toxicity in all breast cancer cell lines. In summary, our study indicated that the isoxazole derivative showed the significant anticancer activity. The results highlight the prospective utility of isoxazole derivatives as new drug candidates for anticancer chemotherapy, suggesting route for the continued exploration and development of drugs suitable for clinical applications.
摘要：
STAT3是七个必需转录因子家族中的关键成员。已经在各种癌症类型中确定了升高的STAT3水平，尤其是在乳腺癌（BC）。因此,抑制STAT3被认为是一种有前途和有效的乳腺癌治疗干预策略.我们在此从胡椒酸[2E，4E)-5-(2H-1,3-苯并二氧杂环戊醇-5-基)戊-2,4-二烯酸]在规定的反应条件下用炔丙基溴,然后用肟处理。从黑胡椒中提取的胡椒碱水解获得胡椒酸。首先,我们通过网络药理学检查了异恶唑衍生物与乳腺癌靶蛋白的结合潜力，分子对接,分子动力学（MD）模拟和细胞毒性分析作为潜在的抗乳腺癌（BC）药物。多源数据库用于鉴定异恶唑衍生物的可能靶标。通过获得与异恶唑衍生物和BC相关的基因符号重叠的877个靶基因，生成了蛋白质-蛋白质相互作用（PPI）网络。分子对接和MD建模证明异恶唑衍生物与必需靶基因之间具有很强的亲和力。Further,异恶唑衍生物在人乳腺癌细胞系上的细胞活力研究显示，在所有乳腺癌细胞系中都有毒性。总之,我们的研究表明，异恶唑衍生物具有显著的抗癌活性。结果突出了异恶唑衍生物作为抗癌化疗新药的潜在用途，为继续探索和开发适合临床应用的药物提供思路。
