Design, synthesis and evaluation of acridine and fused-quinoline derivatives as potential anti-tuberculosis agents

作者：Muscia Gisela C; Buldain Graciela Y; Asis Silvia E^*

来源：European Journal of Medicinal Chemistry, 2014, 73: 243-249.

DOI：10.1016/j.ejmech.2013.12.013

• Mycobacterium tuberculosis
• Acridine derivatives
• Friedlander synthesis
• Inhibitor

The synthesis of twelve acridine and polycyclic acridine derivatives prepared via the Friedlander reaction is described. The one-pot reactions of 2-amino-5-chloro or 5-nitro-benzophenones and a variety of cydanones and indanones were carried out in a MW oven under TFA catalysis in good yields. The products were designed according natural antituberculosis products and were evaluated for growth inhibitory activity towards Mycobacterium tuberculosis H(37)Rv (Mtb) through the National Institute of Allergy and Infectious Diseases (NIAID, USA). Three of them underwent additional testings. The cyclopenta[b]quinoline derivative 9 and the acridine derivative 13 showed remarkable MIC values against the rifampin resistant strain. The former exhibited bactericidal activity at 50 mu g/mL, its intracellular activity is similar to rifampin and it was not cytotoxic at low concentrations so it can be considered a new lead compound.

• 出版日期2014-2-12