Abstract
A series of over a hundred furoxans, alkylnitrates and related compounds were studied as growth inhibitors of the two major kinetoplastids of Latin America, Trypanosoma cruziand Leishmania spp., in in vitro assays. The most active compounds showed 50% inhibitory doses of the same order of that of Nifurtimox and Miltefosine, reference drugs used to treat Chagas Disease and Leishmaniasis respectively. Among the studied compounds derivative 4, presenting excellent inhibitory activity against the tryposmastigote and amastigote forms of T. cruzi, has emerged as a lead compound. Mechanism of action seems to involve mitochondrial dehydrogenases as a distinct effect with respect to Nifurtimox. Excreted metabolites, studied by NMR, showed a significant decrease in succinate, confirming the observed effect on the mitochrondrial dehydrogenases.
References
Apr 1, 1991·Memórias do Instituto Oswaldo Cruz·S G AndradeJ A Grimaud
Jul 30, 1999·Experimental Parasitology·M Almeida-de-FariaM J Alves
Jan 2, 2001·Parasitology Research·S Muelas-SerranoA Gómez-Barrio
Sep 19, 2003·Il Farmaco·I V OvchinnikovA Gasco
Dec 14, 2004·Biochimica Et Biophysica Acta·Paolo AscenziLuigi Gradoni
Mar 28, 2007·Analytica Chimica Acta·A CaligianiV Bocchi
Apr 19, 2007·Journal of Pineal Research·Konstantin ChegaevAlberto Gasco
Aug 19, 2007·Antimicrobial Agents and Chemotherapy·Patricia S DoyleJames H McKerrow
Citations
Jul 3, 2013·European Journal of Medicinal Chemistry·Enrique TorresSilvia Pérez-Silanes
Jan 6, 2012·Parasitology·Diego BenitezHugo Cerecetto
Apr 22, 2011·Journal of Medicinal Chemistry·Diego BenitezAntonio Monge
Mar 21, 2012·Journal of Medicinal Chemistry·Isaac T SchieferGregory R J Thatcher
Jun 25, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Javier VarelaMercedes González
Aug 15, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marcos CoutoMercedes González
Jan 31, 2014·Parasitology·Diego BenítezMercedes González
Nov 23, 2010·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·E M Souza-FagundesO A Martins-Filho
Apr 4, 2017·ChemMedChem·Leonid L Fershtat, Nina N Makhova
Apr 1, 2017·Bioorganic Chemistry·Angel H RomeroSimón E López
Jan 26, 2017·European Journal of Medicinal Chemistry·Angel H RomeroSimón E López
Mar 25, 2010·Pharmaceuticals·Hugo Cerecetto, Mercedes González
Jun 11, 2014·Antimicrobial Agents and Chemotherapy·Luiz Antônio DutraJean Leandro dos Santos
Jun 22, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Mariana FernándezDinorah Gambino
Sep 4, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Letícia de AlmeidaMárcia A S Graminha
Jun 16, 2021·Experimental Parasitology·Letícia Dos Santos PetrySilvia Gonzalez Monteiro
Nov 2, 2021·PloS One·Leandro da Costa ClementinoMarcia A S Graminha