Screening for Anti-Enterovirus Activity of New Diaryl Ethers

Abstract from Fourth National Congress of Virology with International Participation /Days of Virology in Bulgaria Sofia, May 18th - 20th, 2016

Ivanka Nikolova, Adelina Stoyanova, Nadya Nikolova, Petar Grozdanov, Georgi Dobrikov, Angel S. Galabov

The Stephan Angeloff Institute of Microbiology and Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria

Human enteroviruses (EV) are causative agents of a broad spectrum of diseases with extremely high morbidity in children and in the highrisk populations (immunodeficiencies, neonates) which definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. Currently, there is no vaccine available for most EVs except for poliovirus; furthermore, there is a lack of antiviral drugs applied in the clinic for treating EV-induced infections. These shortages reveal the need to develop potent compounds for treating EV infections. Here, we report the result of a screening for anti-enteroviral activity of 64 newly synthetized compounds. The in vitro testing was directed towards poliovirus 1 (PV-1), Coxsackievirus B1 (CVB1) and Coxsackievirus B3 (CVB3) strains, replicated in monolayer HEp-2 cell cultures. The screening included new diaryl ethers synthesized on the base of the molecule of 2-(3, 4-dichlorophenoxy) - 5-nitrobenzonitrile (MDL 860). This compound in previous investigations (Pürstinger et al., 2008) manifested anti-enterovirus activity based on inhibition of an early event in virus replication, right after initial uncoating. Three of the tested MDL 860 related compounds, CB-109, VGA-10-2 and VGA-12-2 demonstrated a marked anti-enteroviral potential - against PV-1 and CVB1, and were inactive vs CVB3. Other two compounds, CB-64 and CB-69 showed a weak effect against CVB3. The start compound, MDL-860 demonstrated a marked effect towards the three enterovirus tested.