Instituto de Tecnología Química (UPV-CSIC), Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Científicas, Avda de los Naranjos s/n, 46022 Valencia, Spain.
Grupo de Investigaciones Dermatológicas, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, 050010 Medellín, Colombia.
J Nat Prod. 2022 Aug 26;85(8):2044-2051. doi: 10.1021/acs.jnatprod.2c00464. Epub 2022 Aug 15.
Viral infections affect several million patients annually. Although hundreds of viruses are known to be pathogenic, only a few can be treated in the clinic with available antiviral drugs. Naturally based pharmacotherapy may be a proper alternative for treating viral diseases. Several natural and semisynthetic abietane-type diterpenoids have shown important antiviral activities. In this study, a biological evaluation of a number of either C-18- or C-19-functionalized known semisynthetic abietanes against , , 1, and are reported. Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol displayed broad-spectrum antiviral properties. The scale-up synthesis of this analogue has been optimized for further studies and development. This molecule displayed an EC between 5.0 and 10.0 μM against Colombian Zika virus strains and EC = 9.8 μM against Chikungunya virus. Knowing that this ferruginol analogue is also active against 2 (EC = 1.4 μM, DENV-2), we can conclude that this compound is a promising broad-spectrum antiviral agent paving the way for the development of novel antivirals.
病毒感染每年影响数百万患者。尽管已知有数百种病毒具有致病性，但临床上仅可用现有抗病毒药物治疗少数几种病毒。基于天然的药物疗法可能是治疗病毒性疾病的合适选择。一些天然和半合成枞型二萜类化合物已显示出重要的抗病毒活性。在这项研究中，报告了对一些 C-18-或 C-19-功能化的已知半合成枞酸进行的生物学评估，包括对,, 1, 和 。半合成枞酸铁杉醇及其类似物 18-（邻苯二甲酰亚胺-2-基）铁杉醇显示出广谱抗病毒特性。该类似物的放大合成已针对进一步的研究和开发进行了优化。该分子对哥伦比亚寨卡病毒株的 EC 值在 5.0 和 10.0 μM 之间，对基孔肯雅病毒的 EC 值为 9.8 μM。鉴于该铁杉醇类似物也对 2（EC = 1.4 μM，DENV-2）有效，我们可以得出结论，该化合物是一种有前途的广谱抗病毒药物，为开发新型抗病毒药物铺平了道路。
