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

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• 作者：Claudia Mara Maciel-Rezende^a ; ^b ; Letí ; cia de Almeida^c ; ^d ; É ; derson D&rsquo ; Martin Costa^b ; Francieli Ribeiro Pires^a ; Karina Ferreira Alves^d ; Clá ; udio Viegas Junior^a ; ^e ; Danielle Ferreira Dias^a ; ^e ; Antô ; nio Carlos Doriguetto^e ; Marcos José ; Marques^d ; ^f ; Marcelo Henrique dos Santos^a ; ^g ; ^{marcelo_hs@yahoo.com.br}
• 关键词：Benzophenone derivatives ; Leishmaniasis ; Leishmania amazonensis
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 June, 2013
• 年：2013
• 卷：21
• 期：11
• 页码：3114-3119
• 全文大小：571 K

文摘

Nine O-alkyl and O-prenyl derivatives were synthesized from commercial 2,4-dihydroxybenzophenone, 4,e4,4¡ä-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¡ä-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.