Synthesis and antifungal activity of substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles

Series of substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles derivatives have been synthesized and examined for their activity against pathogenic strains of Aspergillus fumigatus (ITCC 4517), Aspergillus flavus (ITCC 5192) Aspergillus niger (ITCC 5405) and Candida albicans (ITCC No 4718). All synthesized compounds showed mild to moderate activity, except for 2-substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles 6a–d. The most active 1-(4-chlorophenyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole 4c exhibited a MIC value of 5.85 μg/disc against A. fumigatus and 11.71 μg/disc against A. flavus and A. niger in disc diffusion assay. Anti-Aspergillus activity of active compound 4c by microbroth dilution assay was found to be 15.62 μg/ml in case of A. fumigatus and 31.25 μg/ml with A. flavus and A. niger. The MIC90 value of the most active compound by percent germination inhibition assay was found to be 15.62 μg/ml against A. fumigatus. The MIC90 values of substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indoles against C. albicans ranged from 15.62 to 250 μg/ml. The in vitro toxicity of the most active 1-(4-chlorophenyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole 4c was evaluated using haemolytic assay, in which the compound was found to be non-toxic to human erythrocytes up to a concentration of 312.50 μg/ml. The standard drug amphotericin B exhibited 100% lysis at a concentration of 37.5 μg/ml.

Synthesis and antifungal activity studies on substituted-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole derivatives against pathogenic strains of Aspergilli and Candida albicans reveal that 1-(4-chlorophenyl)-10-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole 4c is the most active compound and was found to be less toxic than the standard drug amphotericin B up to the tested concentration, that is, 10,000.0 μg/ml and lysed only 43.75% of human erythrocytes.Figure optionsDownload as PowerPoint slide