In vitro anti-BK polyomavirus activity of imidazo[1,2-c]pyrimidine and pyrimido[1,6 a]pyrimidine derivatives

• Main Authors: Roman Solomyannyi, Oleg Mitiukhin, Mark Prichard, Scott James, Carol Hartline, Victor Zhirnov, Volodymyr Brovarets
• Format: Article
• Language: English
• Published: Growing Science 2019-10-01
• Series: Current Chemistry Letters
• Subjects: Antiviral activity; pyrimidine derivatives; BK polyomavirus; heterocycles; cyclizatio
• Online Access: http://www.growingscience.com/ccl/Vol9/ccl_2019_29.pdf

Five imidazo[1,2-c]pyrimidine and pyrimido[1,6-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiproliferative activity and cytotoxicity. Primary bioassays in vitro showed that two of five synthesized compounds, 6-benzyl-8-(methylsulfonyl)-2,6-dihydroimidazo[1,2-c]pyrimidin-5(3H)-one, and 9-(methylsulfonyl)-7-propyl-2,3,4,7-tetrahydro-6H-pyrimido[1,6-a]pyrimidin-6-one possessed potent antiviral activity against BKV (EC50: 0.66 μM and 0.96, respectively). The selectivity index of these compounds is similar to that of cidofovir. Although antiviral activity was evident in secondary assays, significant virus inhibition occurred at or near the cytotoxic concentration (SI90=1). Here we show that substituted pyrimidine derivatives are a promising structure class of chemical compounds for the development of antiviral drugs against BKV infections. Hence these compounds may be taken as lead compounds for further development of novel antimicrobial and anticancer agents.