title: Synthesis and biological evaluation against Leishmania amazonensis of a series of alkyl-substituted benzophenones.
abstract: Nine O-alkyl and O-prenyl derivatives were synthesized from commercial 2,4-dihydroxybenzophenone, 4,e4,4'-dihydroxybenzophenone and were evaluated for their leishmanicidal activity against promastigote forms of Leishmania amazonensis, as well their toxicity in murine macrophages. All derivatives exhibited better biological activity than their hydroxylated benzophenones precursors, and new compound LFQM-123 (3c) was 250-fold more active than its precursor 4,4'-dihydroxybenzophenone (3). Moreover, some of the results were comparable to the standard drug Amphotericin B, suggesting that the increase in lipophilicity could facilitate protozoa membrane permeation. In this study we confirmed that benzophenone derivatives exhibit leishmanicidal properties, with relatively low toxicity, and thus could be exploited as promise prototypes for the design and development of new drug for the treatment of leishmaniasis.
authors.affiliation: Laboratório de Fitoquímica e Química Medicinal, Universidade Federal de Alfenas, 37130-000 Alfenas, MG, Brazi.
authors.forename: Claudia Mara
authors.initials: CM
authors.lastname: Maciel-Rezende
authors.forename: Letícia
authors.initials: L
authors.lastname: de Almeida
authors.forename: Éderson D'Martin
authors.initials: ÉD
authors.lastname: Costa
authors.forename: Francieli Ribeiro
authors.initials: FR
authors.lastname: Pires
authors.forename: Karina Ferreira
authors.initials: KF
authors.lastname: Alves
authors.forename: Cláudio
authors.initials: C
authors.lastname: Viegas
authors.forename: Danielle Ferreira
authors.initials: DF
authors.lastname: Dias
authors.forename: Antônio Carlos
authors.initials: AC
authors.lastname: Doriguetto
authors.forename: Marcos José
authors.initials: MJ
authors.lastname: Marques
authors.forename: Marcelo Henrique
authors.initials: MH
authors.lastname: dos Santos
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D001577:Benzophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development; D008018:Life Cycle Stages / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001577:Benzophenones; D014344:Trypanocidal Agents; D000666:Amphotericin B; C121479:2,4-dihydroxybenzophenone