Shi Wei, Nacev Benjamin A, Bhat Shridhar, Liu Jun O
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
ACS Med Chem Lett. 2010;1(4):155-159. doi: 10.1021/ml1000068.
Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (1a-1h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans- stereoisomers, especially 1e and 1f, suggest different molecular mechanisms underlying the anti-angiogenic and anti-fungal activities of itraconazole.
伊曲康唑在临床上用作抗真菌剂，最近已被证明具有抗血管生成活性。伊曲康唑有三个手性中心，可产生八种立体异构体。然而，立体化学在伊曲康唑这两种活性中的完整作用尚未得到充分探讨。首次合成了伊曲康唑的所有八种立体异构体（1a - 1h），并评估了它们对人内皮细胞增殖的活性以及对五种真菌菌株的抗真菌活性。反式立体异构体，特别是1e和1f，具有明显不同的抗血管生成和抗真菌活性谱，这表明伊曲康唑的抗血管生成和抗真菌活性背后存在不同的分子机制。
