Abstract：
Cassava extracts containing cyanogenic compounds demonstrate anticancer properties. The cyanogenic glucoside linamarin found abundantly in cassava can release hydrogen cyanide (HCN) upon hydrolysis, a potent cytotoxin. However, linamarin\'s hydrolysis mechanism by human enzymes is poorly delineated and constitutes a bottleneck for therapeutic development. This study aimed to investigate linamarin\'s hydrolysis mechanism by human β-glucosidase and identify structural derivatives with enhanced hydrolytic potential using density functional theory calculations. Results revealed α-anomeric derivatives as promising, with leaving group ability and steric bulk strongly governing hydrolysability. We identified several linamarin analogs with predicted rapid hydrolysis kinetics that may enable swift cytotoxic HCN release against cancer cells. This investigation enriches understanding of cyanogenic glycoside reactivity to facilitate their development as targeted antineoplastic agents. The identified derivatives set the groundwork for experimental evaluation of enhanced linamarin-inspired compounds as innovative cancer therapeutics.
摘要：
含有生氰化合物的木薯提取物具有抗癌特性。木薯中大量发现的氰化葡糖苷linamarin可以在水解时释放氰化氢（HCN），一种强效的细胞毒素.然而,linamarin通过人类酶的水解机制描述得很差，并构成了治疗发展的瓶颈。本研究旨在研究人β-葡萄糖苷酶对linamarin的水解机理，并使用密度泛函理论计算确定具有增强水解潜力的结构衍生物。结果表明，α-异头衍生物是有前途的，离去基团能力和空间体积强烈控制水解性。我们确定了几种具有预测的快速水解动力学的linamarin类似物，可以使针对癌细胞的快速细胞毒性HCN释放。这项研究丰富了对氰苷反应性的理解，以促进其作为靶向抗肿瘤剂的发展。确定的衍生物为增强的linamarin启发化合物作为创新癌症疗法的实验评估奠定了基础。
