Synthesis and evaluation of novel chromanone and quinolinone analogues of uniflorol as anti-leishmanial agents
Helena Castro,
Tânia Cruz,
Patrícia de Aguiar Amaral,
Paula da Silva Cardoso,
Ahmed Alsaffar,
Patrick Farrell,
Ana M. Tomás,
James W. Barlow
Affiliations
Helena Castro
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
Tânia Cruz
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
Patrícia de Aguiar Amaral
Laboratory of Medicinal Plants (LaPlaM/ PPGCA), Universidade do Extremo Sul Catarinense (UNESC), Avenida Universitária 1105, Bairro Universitário, 88806-000 Criciúma, SC, Brazil
Paula da Silva Cardoso
Laboratory of Medicinal Plants (LaPlaM/ PPGCA), Universidade do Extremo Sul Catarinense (UNESC), Avenida Universitária 1105, Bairro Universitário, 88806-000 Criciúma, SC, Brazil; Department of Chemistry, RCSI, 123 St. Stephen's Green, Dublin 2, Ireland
Ahmed Alsaffar
Department of Chemistry, RCSI, 123 St. Stephen's Green, Dublin 2, Ireland
Patrick Farrell
Department of Chemistry, RCSI, 123 St. Stephen's Green, Dublin 2, Ireland
Ana M. Tomás
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
James W. Barlow
Department of Chemistry, RCSI, 123 St. Stephen's Green, Dublin 2, Ireland; Corresponding author.
Within this work, we describe the design and synthesis of a range of novel chromanones and quinolinones, based on natural products reported to possess anti-leishmanial action. The core heterocycles were obtained either via classical or ionic liquid mediated Kabbe condensation in the case of chromanones, or aqueous Sonogashira based alkynylation followed by acid-catalysed cyclisation in the case of quinolinones. Upon testing in promastigotes, axenic amastigotes and Leishmania-infected macrophages, compound 13c was identified as displaying interesting activity, inhibiting axenic amastigotes and intracellular amastigotes with IC50s of 25.3 and 24.6μM respectively.