Departamento de Química Orgánica, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain.
Laboratorio de Microbiología Molecular, Instituto de Investigación Hospital 12 de Octubre (imas12), 28041 Madrid, Spain.
Int J Mol Sci. 2022 May 3;23(9):5083. doi: 10.3390/ijms23095083.
The synthesis of new biocompatible antiviral materials to fight against the development of multidrug resistance is being widely explored. Due to their unique globular structure and excellent properties, [60]fullerene-based antivirals are very promising bioconjugates. In this work, fullerene derivatives with different topologies and number of glycofullerene units were synthesized by using a SPAAC copper free strategy. This procedure allowed the synthesis of compounds -, containing from 20 to 40 mannose units, in a very efficient manner and in short reaction times under MW irradiation. The glycoderivatives were studied in an infection assay by a pseudotyped viral particle with Ebola virus GP1. The results obtained show that these glycofullerene oligomers are efficient inhibitors of EBOV infection with ICs in the nanomolar range. In particular, compound , with four glycofullerene moieties, presents an outstanding relative inhibitory potency (RIP). We propose that this high RIP value stems from the appropriate topological features that efficiently interact with DC-SIGN.
正在广泛探索合成新的生物相容性抗病毒材料以对抗多药耐药性的发展。由于其独特的球形结构和优异的性能，基于富勒烯的抗病毒药物是非常有前途的生物缀合物。在这项工作中，通过无铜 SPAAC 策略合成了具有不同拓扑结构和糖基富勒烯单元数目的富勒烯衍生物。该方法允许以非常有效的方式和在 MW 辐射下的短反应时间合成化合物 - ，其包含 20 至 40 个甘露糖单元。糖衍生物通过具有埃博拉病毒 GP1 的假病毒颗粒进行感染测定进行研究。得到的结果表明，这些糖基富勒烯低聚物是埃博拉病毒感染的有效抑制剂，IC 在纳摩尔范围内。特别是，具有四个糖基富勒烯部分的化合物 - ，表现出出色的相对抑制效力（RIP）。我们提出，这种高 RIP 值源于与 DC-SIGN 有效相互作用的适当拓扑特征。
