molecules Communication The Evolution of Pleconaril: Modified O-Alkyl Linker Analogs Have Biological Activity towards Coxsackievirus B3 Nancy 1, 2, 1 3 Alexandrina Volobueva y, Anna Egorova y, Anastasia Galochkina , Sean Ekins , Vladimir Zarubaev 1 and Vadim Makarov 2,* 1 Saint-Petersburg Pasteur Institute, Mira str., 14, 197101 Saint Petersburg, Russia;
[email protected] (A.V.);
[email protected] (A.G.);
[email protected] (V.Z.) 2 Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky prospect, 33, build. 2, 119071 Moscow, Russia;
[email protected] 3 Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, NC 27606, USA;
[email protected] * Correspondence:
[email protected] These authors contributed equally to this work. y Received: 10 February 2020; Accepted: 13 March 2020; Published: 16 March 2020 Abstract: Coxsackieviruses type B are one of the most common causes of mild upper respiratory and gastrointestinal illnesses. At the time of writing, there are no approved drugs for effective antiviral treatment for Coxsackieviruses type B. We used the core-structure of pleconaril, a well-known antienteroviral drug candidate, for the synthesis of novel compounds with O-propyl linker modifications. Some original compounds with 4 different linker patterns, such as sulfur atom, ester, amide, and piperazine, were synthesized according to five synthetic schemes. The cytotoxicity and bioactivity of 14 target compounds towards Coxsackievirus B3 Nancy were examined. Based on the results, the values of 50% cytotoxic dose (CC50), 50% virus-inhibiting dose (IC50), and selectivity index (SI) were calculated for each compound. Several of the novel synthesized derivatives exhibited a strong anti-CVB3 activity (SI > 20 to > 200).