Synthesis and anti-Mycobacterium tuberculosis activity of imide- β-carboline and carbomethoxy-β-carboline derivatives.

Synthesis and anti-Mycobacterium tuberculosis activity of imide-β-carboline and carbomethoxy-β-carboline derivatives. Eur J Med Chem. 2019 Dec 04;187:111935 Authors: Lopes-Ortiz MA, Panice MR, Borges de Melo E, Ataide Martins JP, Baldin VP, Agostinho Pires CT, Caleffi-Ferracioli KR, Dias Siqueira VL, Bertin de Lima Scodro R, Sarragiotto MH, Cardoso RF Abstract A series of methyl β-carboline carboxylates (2a-g) and of imide-β-carboline derivatives containing the phthalimide (4a-g), maleimide (5b, g) and succinimide (6b, e, g) moiety were synthesized, and evaluated for their activity against Mycobacterium tuberculosis H37Rv. The most active β-carboline derivatives against the reference strain were assayed for their cytotoxicity and the activity against resistant M. tuberculosis clinical isolates. Farther, structure-activity relationship (SAR) studies were carried out using the three and four-dimensional approaches for starting to understand the way of β-carboline activity in M. tuberculosis. All 19 β-carboline derivatives were assayed, firstly, by determining the minimum inhibitory concentration (MIC) using resazurin microtiter assay plate (REMA) in M. tuberculosis H37Rv. Then, five derivatives (2c, 4a, 4e, 4g, 6g), which showed MIC ≤ 125 μg/mL, were assayed in nine resistant M. tuberculosis clinical isolates (five MDR, three isoniazid monoresistant and one isoniazid plus streptomycin resistant). The MIC values against...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research