A minimalistic approach to develop new anti-apicomplexa polyamines analogs

PANOZZO-ZÉNERE, ESTEBAN A.; PORTA, EXEQUIEL O.J.; ARRIZABALAGA, GUSTAVO; FARGNOLI, LUCÍA; KHAN, SHABANA I.; TEKWANI, BABU L.; LABADIE, GUILLERMO R.

EUROPEAN JOURNAL OF MEDICAL CHEMISTRY

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2018 vol. 143 p. 866 - 880

0223-5234

The development of new chemical entities against the major diseases caused by parasites is highly desired. A library of thirty diamines analogs following a minimalist approach and supported by chemoinformatics tools have been prepared and evaluated against apicomplexan parasites. Different member of the series of N,N´-disubstituted aliphatic diamines shown in vitro activities at submicromolar concentrations and high levels of selectivity against Toxoplasma gondii and in chloroquine-sensitive and resistant-strains of Plasmodium falciparum. In order to demonstrate the importance of the secondary amines, ten N,N,N´,N´-tetrasubstituted aliphatic diamines derivatives were synthesized being considerably less active than their disubstituted