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A-和AB-氟代卟啉:合成、X射线表征及抗人巨细胞病毒感染的抗病毒活性评估

A- and AB-fluorocorroles: synthesis, X-ray characterization and antiviral activity evaluation against human cytomegalovirus infection.

作者信息

Kappler-Gratias Sandrine, Bucher Léo, Desbois Nicolas, Rousselin Yoann, Bystricky Kerstin, Gros Claude P, Gallardo Franck

机构信息

NeoVirTech , SAS , Institut des Technologies Avancées en sciences du Vivant (CNRS USR3505) , 1 place Pierre Potier, Oncopole , 31106 Toulouse , France . Email:

Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB) , UMR CNRS 6302 , Université Bourgogne Franche-Comté , 9 Avenue Alain Savary, BP 47870 , 21078 Dijon Cedex , France . Email:

出版信息

RSC Med Chem. 2020 Jul 13;11(7):783-801. doi: 10.1039/d0md00127a. eCollection 2020 Jul 1.

Abstract

Twenty-nine fluorinated corroles were prepared, spectroscopically characterized, and studied for their antiviral activity against human cytomegalovirus infection. Six corroles were also fully characterized by X-ray crystallography giving insights on their geometrical features. The halogenated corroles reported herein exhibit significantly improved antiviral activity over their non-halogenated counterparts and over nitro-corrole analogs previously reported. Full activity of thirteen A-corroles is achieved with four fluorine atoms present on the -phenyl ring reaching a selectivity index above 300. The maximum activity is achieved for AB-corroles with selectivity indexes above 400. We thus demonstrate that the fluorocorrole is a highly potent platform to synthesize a new generation of anti hCMV molecules.

摘要

制备了29种氟化卟啉,通过光谱对其进行了表征,并研究了它们对人巨细胞病毒感染的抗病毒活性。其中6种卟啉还通过X射线晶体学进行了全面表征,从而深入了解了它们的几何特征。本文报道的卤代卟啉比其未卤代的同类物以及先前报道的硝基卟啉类似物具有显著提高的抗病毒活性。当β-苯环上存在四个氟原子时,13种A-卟啉实现了完全活性,选择性指数超过300。对于AB-卟啉,选择性指数高于400时可实现最大活性。因此,我们证明氟代卟啉是合成新一代抗人巨细胞病毒分子的高效平台。

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