Exploring 4,7-Disubstituted Pyrimido[4,5-<i>d</i>]pyrimidines as Antiviral and Anticancer Agents
Eleftheria A. Georgiou,
Konstantinos Paraskevas,
Christina Koutra,
Leentje Persoons,
Dominique Schols,
Steven De Jonghe,
Ioannis K. Kostakis
Affiliations
Eleftheria A. Georgiou
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Konstantinos Paraskevas
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Christina Koutra
Department of Pharmacy, Division of Pharmacognosy and Natural Products Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Leentje Persoons
Molecular Genetics and Therapeutics in Virology and Oncology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium
Dominique Schols
Molecular Structural and Translational Virology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium
Steven De Jonghe
Molecular Structural and Translational Virology Research Group, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, P.O. Box 1043, 3000 Leuven, Belgium
Ioannis K. Kostakis
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece
Thirteen new 4,7-disubstituted pyrimido[4,5-d]pyrimidines were synthesized via a straightforward methodology starting from thiourea. The anti-proliferative activity of these compounds was evaluated across a diverse panel of eight cancer cell lines, with derivatives 7d and 7h showing efficacy against several hematological cancer types. Furthermore, all compounds were assessed for their antiviral potency against a panel of viruses. Compounds featuring a cyclopropylamino group and an aminoindane moiety exhibited remarkable efficacy against human coronavirus 229E (HCoV-229E). These findings highlight the pyrimidino[4,5-d]pyrimidine scaffold as an interesting framework for the design of novel antiviral agents against HCoVs, with compounds 7a, 7b, and 7f emerging as strong candidates for further investigation.
