Property-based design and synthesis of new chloroquine hybrids via simple incorporation of 2-imino-thiazolidin-4-one or 1h-pyrrol-2, 5-dione fragments on the 4-amino-7-chloroquinoline side chain

• Autor(a) principal: Rojas,Fernando A
• Data de Publicação: 2011
• Outros Autores: Kouznetsov,Vladimir V
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532011000900021
• topic: 4-amino-7-chloroquinolines; 2-imino-thiazolidin-4-ones; 1H-pyrrol-2,5-diones; molecular hybrids; property-based design; drug-like properties; antimalarial agents

In the present work, the syntheses of new 4-amino-7-chloroquinoline N-derivatives were performed by selective modification of the side chain amino group of N-(7-chloroquinolin-4-yl) alkyldiamines, basis framework of chloroquine (CQ) drug through the incorporation of heterocyclic 2-imino-thiazolidin-4-one and 1H-pyrrol-2,5-dione systems. These potential activity modulators were selected thanks to their characteristic properties, and evaluated by virtual screening employing the OSIRIS and Molinspirations platforms. Designed and synthesized quinolinic derivatives could increase the antimalarial activity of CQ analogues without affecting the lipophilicity as described in literature, suggesting them as candidates for further biological assessments.