1.Differential effects of the putative GBF1 inhibitors Golgicide A and AG1478 on enterovirus replication.
van der Linden L1, van der Schaar HM, Lanke KH, Neyts J, van Kuppeveld FJ. J Virol. 2010 Aug;84(15):7535-42. doi: 10.1128/JVI.02684-09. Epub 2010 May 26.
The genus Enterovirus, belonging to the family Picornaviridae, includes well-known pathogens, such as poliovirus, coxsackievirus, and rhinovirus. Brefeldin A (BFA) impedes replication of several enteroviruses through inhibition of Golgi-specific BFA resistance factor 1 (GBF1), a regulator of secretory pathway integrity and transport. GBF1 mediates the GTP exchange of Arf1, which in activated form recruits coatomer protein complex I (COP-I) to Golgi vesicles, a process important in transport between the endoplasmic reticulum and Golgi vesicles. Recently, the drugs AG1478 and Golgicide A (GCA) were put forward as new inhibitors of GBF1. In this study, we investigated the effects of these putative GBF1 inhibitors on secretory pathway function and enterovirus replication. We show that both drugs induced fragmentation of the Golgi vesicles and caused dissociation of Arf1 and COP-I from Golgi membranes, yet they differed in their effect on GBF1 localization.
2.Distinct biological effects of golgicide a derivatives on larval and adult mosquitoes.
Mack DJ1, Isoe J, Miesfeld RL, Njardarson JT. Bioorg Med Chem Lett. 2012 Aug 15;22(16):5177-81. doi: 10.1016/j.bmcl.2012.06.076. Epub 2012 Jul 5.
A collection of Golgicide A (GCA) analogs has been synthesized and evaluated in larval and adult mosquito assays. Commercially available GCA is a mixture of four compounds. One enantiomer (GCA-2) of the major diastereomer in this mixture was shown to be responsible for the unique activity of GCA. Structure-activity studies (SAR) of the GCA architecture suggested that the pyridine ring was most easily manipulated without loss or gain in new activity. Eighteen GCA analogs were synthesized of which five displayed distinct behavior between larval and adult mosquitos, resulting in complete mortality of both Aedes aegypti and Anopheles stephensi larvae. Two analogs from the collection were shown to be distinct from the rest in displaying high selectivity and efficiency in killing An. stephensi larvae.