設計及合成L-苯丙胺酸衍生物對抗SARS-CoV 3CL蛋白酶

Abstract

西元2002年，廣東省爆發第一起SARS感染病例。短短數個月內，已經造成近千人的死亡，由SARS冠狀病毒引起的死亡率相當高，大約是10%。 我們發現L-苯丙胺酸衍生物擁有高度抗SARS的活性，如果化合物由2-氯基，4-硝基苯胺，L-苯丙胺酸，4-二甲基胺基苯甲酸組成，擁有高度抗SARS活性，IC50的數值是0.06microM。L-苯丙胺酸的硼酸酯衍生物也具有抗SARS活性，目前把硼酸酯類化合物水解得到的硼酸類化合物，用來作對抗SARS的抑制劑。

Severe Acute Respiratory Syndrome (SARS) first occurred in Guandong (China) in November of 2002. In only a few months, nearly 1000 lives were claimed. The fatality rate of SARS coronavirus infection is rather high, estimated to be 10%. We found the phenylalanine derivatives possessed good inhibitory activities. The compound prepared from 2-chloro-4-nitroaniline, L-phenylalanine, and 4-(dimethylamino)benzoic acid is the most potent inhibitor, showing an IC50 of 0.06 μM. The boronate analog of L-phenylalanine also showed inhibitory activities. We currently conduct the hydrolysis to remove the pinanediol moiety in order to get the boronic acid compounds as the transition state mimics of phenylalinine, and evaluate their anti-SARS activity.