Esteban A Panozzo-Zénere1, Exequiel O J Porta1, Gustavo Arrizabalaga2, Lucía Fargnoli1, Shabana I Khan3, Babu L Tekwani3, Guillermo R Labadie4. 1. Instituto de Química Rosario (IQUIR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina. 2. Departments of Microbiology and Immunology, Indiana University, School of Medicine, Indianapolis, IN 46202, USA. 3. National Center for Natural Products Research & Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, MS 38677, USA. 4. Instituto de Química Rosario (IQUIR-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina; Departamento de Química Orgánica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK, Rosario, Argentina. Electronic address: labadie@iquir-conicet.gov.ar.
Abstract
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 counterpart. Theoretical studies were performed to establish the electronic factors that govern the activity of the compounds.
The development of new chemical entities against the major diseases caused by parasites is highly desired. A librn class="Chemical">ary 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'-disubstitutedaliphatic 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'-tetrasubstitutedaliphatic diamines derivatives were synthesized being considerably less active than their disubstituted counterpart. Theoretical studies were performed to establish the electronic factors that govern the activity of the compounds.
Authors: Exequiel O J Porta; Paulo B Carvalho; Mitchell A Avery; Babu L Tekwani; Guillermo R Labadie Journal: Steroids Date: 2013-11-04 Impact factor: 2.668
Authors: Aaron Muth; Joseph Kamel; Navneet Kaur; Allyson C Shicora; Iraimoudi S Ayene; Susan K Gilmour; Otto Phanstiel Journal: J Med Chem Date: 2013-07-10 Impact factor: 7.446