Zhou Shiwen, Zheng Qingfei, Huang Xiuyong, Wang Yong, Luo Sifan, Jiang Renwang, Wang Lei, Ye Wencai, Tian Haiyan
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Org Biomol Chem. 2017 Jul 5;15(26):5609-5615. doi: 10.1039/c7ob01055a.
Three pairs of bufadienolide l/d-lactate epimers (1-6) were isolated from the eggs of the toad Bufo bufo gargarizans. The structures were elucidated by using spectroscopic methods, X-ray diffraction analysis and a modified Mosher's method. Compounds 1-6 represent the first occurrence of lactate-conjugated bufadienolides in nature, and illustrate the existence of an enzyme-controlled epimerization from l- to d-lactate in amphibians. The biosynthetic pathways, in which two key enzymes might be involved (i.e., lactate racemase and acyltransferase), were proposed. In addition, the biological assays revealed that compounds 1-4 are potent cytotoxic agents against human gastric cancer cells BGC-823 and human lung cancer cells A549 with IC values in a range of 8.0 to 80.0 nM.
从中华大蟾蜍的卵中分离出三对蟾毒配基l/d-乳酸差向异构体（1-6）。通过光谱方法、X射线衍射分析和改良的莫舍尔方法阐明了其结构。化合物1-6是自然界中首次出现的乳酸共轭蟾毒配基，说明了两栖动物中存在从l-乳酸到d-乳酸的酶控差向异构化。提出了可能涉及两种关键酶（即乳酸消旋酶和酰基转移酶）的生物合成途径。此外，生物活性测定表明，化合物1-4是针对人胃癌细胞BGC-823和人肺癌细胞A549的强效细胞毒剂，IC值在8.0至80.0 nM范围内。
