Multicomponent Synthesis of Diaminopurine and Guanine PNA's Analogues Active against Influenza A Virus from Prebiotic Compounds

Bruno Mattia Bizzarri; Angelica Fanelli; Stefania Ciprini; Alessandra Giorgi; Marta De Angelis; Raoul Fioravanti; Lucia Nencioni; Raffaele Saladino

doi:10.1021/acsomega.2c05754

Multicomponent Synthesis of Diaminopurine and Guanine PNA's Analogues Active against Influenza A Virus from Prebiotic Compounds

ACS Omega. 2022 Nov 29;7(49):45253-45264. doi: 10.1021/acsomega.2c05754. eCollection 2022 Dec 13.

Authors

Bruno Mattia Bizzarri¹, Angelica Fanelli¹, Stefania Ciprini¹, Alessandra Giorgi¹, Marta De Angelis², Raoul Fioravanti², Lucia Nencioni², Raffaele Saladino¹

Affiliations

¹ Department of Biological and Ecological Sciences, University of Tuscia, Viterbo 01100, Italy.
² Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome 00185, Italy.

Abstract

Peptide nucleic acids (PNAs) play a key role in prebiotic chemistry as a chimera between RNA and proteins. We developed an alternative synthesis of bioactive PNA's diaminopurine and guanine analogues from prebiotic compounds, such as aminomalononitrile (AMN), urea, and guanidine, using a two-step multicomponent microwave-assisted and solvent-free approach in the presence of selected amino acids. The novel derivatives showed selective inhibitory activity against influenza virus A/Puerto Rico/8/34 H1N1 encompassing the range of nanomolar activity. Derivatives decorated with the tyrosine residue showed the highest inhibitory activity against the virus.