芹菜素
前药
碱性磷酸酶
化学
药理学
体内
磷酸酶
生物化学
癌症研究
磷酸化
酶
医学
生物
类黄酮
抗氧化剂
生物技术
作者
Dimitrios Diamantis,Antonios D. Tsiailanis,Christina Papaemmanouil,Maria‐Christina Nika,Zoi Kanaki,Simona Golič Grdadolnik,Andréj Babič,Eleftherios Paraskevas Tzakos,Isabelle Fournier,Michel Salzet,Prem Prakash Kushwaha,Nikolaos S. Thomaidis,Θεόδωρος Ράμπιας,Eswar Shankar,Serdar Karakurt,Sanjay Gupta,Andreas G. Tzakos
标识
DOI:10.1080/07391102.2023.2247083
摘要
Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors.Communicated by Ramaswamy H. Sarma
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