Carbonic anhydrase IX (CAIX) is an emerging drug target for hypoxia associated cancers. To identify potent and selective inhibitors of CAIX, a small library of ferulic acid (FA) derivatives bearing triazole moiety has been designed, synthesized and evaluated against different human CA isoforms (CAII, CAVA & CAIX). Though most of the compounds showed CAIX inhibition in the micromolar range, compound 7i selectively inhibits CAIX in the nanomolar range (IC₅₀= 24 nM). In silico analysis revealed binding of 7i with the catalytically important amino acid residues of CAIX. Further, cell-based studies indicate that 7i inhibits the activity of CAIX, decreases the epithelial to mesenchymal transitions, induces apoptosis, inhibits cell migration and colonization potential of cancer cells. Taken together, these results emphasized the use of 7i as a prospective pharmacological lead molecule in CAIX targeted anticancer therapeutics.

碳酸酐酶IX（CAIX）是与缺氧相关的癌症的新兴药物靶标。为了鉴定CAIX的有效和选择性抑制剂，已经设计，合成并针对不同的人类CA同工型（CAII，CAVA和CAIX）评估了一个带有三唑部分的小分子阿魏酸（FA）衍生物。尽管大多数化合物在微摩尔范围内均显示出CAIX抑制作用，但化合物7i在纳摩尔范围内（IC ₅₀ = 24 nM）选择性抑制了CAIX 。在计算机分析中发现7i与CAIX的催化重要的氨基酸残基结合。此外，基于细胞的研究表明7i抑制CAIX的活性，减少上皮到间质的转变，诱导细胞凋亡，抑制癌细胞的迁移和定殖能力。综上所述，这些结果强调了7i作为CAIX靶向抗癌治疗剂中的前瞻性药理学先导分子的用途。