Synthesis and biological evaluation against Leishmania amazonensis of a series of alkyl-substituted benzophenones

• Published in: Bioorganic & medicinal chemistry 2013-06, Vol.21 (11), p.3114-3119
• Main Authors: Maciel-Rezende, Claudia Mara, de Almeida, Letícia, Costa, Éderson D’Martin, Pires, Francieli Ribeiro, Alves, Karina Ferreira, Junior, Cláudio Viegas, Dias, Danielle Ferreira, Doriguetto, Antônio Carlos, Marques, Marcos José, dos Santos, Marcelo Henrique
• Format: Article
• Language: English
• Subjects: amphotericin B; Amphotericin B - pharmacology; Animals; benzophenone; Benzophenone derivatives; Benzophenones - chemical synthesis; Benzophenones - chemistry; Benzophenones - pharmacology; Cell Membrane Permeability; Cell Survival - drug effects; Cells, Cultured; drug therapy; drugs; hydrophobicity; Leishmania amazonensis; Leishmania mexicana - drug effects; Leishmania mexicana - growth & development; Leishmaniasis; Life Cycle Stages - drug effects; macrophages; Macrophages, Peritoneal - drug effects; Mice; prototypes; Structure-Activity Relationship; toxicity; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - pharmacology
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.03.045

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.