Synthesis and antitubercular activityin vitro of tetrahydrocarbazole derivatives. I. N-substituted hexahydro-1H-pyrazino [3,2,1-j,k] carbazoles

Novel Pyridazino[4,3-b]indoles with Dual Inhibitory Activity against Mycobacterium tuberculosis and Monoamine Oxidase

“…We have long considered that the relationship between the antituberculosis and the MAO inhibitory action of such compounds as pyridazinoindoles is not fortuitous in that simultaneous manifestation of antipsychotic, anti-MAO, and antituberculosis activities is typical for some classes of N,N-containing compounds and fused indoles. − ,, However, there is no consistent correlation between inhibition of M. tuberculosis and MAO activity. In the case of the bromo-substituted pyridazinoindoles such as 4l and 5l , 4k and 5k , we conclude that the insertion of a bromo substituent changes not only electronic effects but also topographical features of the structures.…”

“…32 Isolated mitochondria were washed and suspended in 50 mM phosphate buffer, pH 7.4, and stored at -20 °C. MAO activity was assayed radiometrically by accumulation of 14 C-labeled aldehydes formed during enzymatic deamination of 14 C-labeled amines. 32 [ 14 C]-5-Hydroxytryptamine creatinine sulfate (0.1 mM) and [ 14 C]-phenylethylamine (10 µM) were used as substrates of MAO-A and MAO-B, respectively.…”

“…13 Several original Russian antidepressants and reversible MAO inhibitors, such as pirlindole and tetrindol, exhibited marked antituberculosis activity. 14 The MAO inhibitor isocarboxazide (marplan), used in psychiatry, and its close analogue 5-methylisoxazole-3-carboxylic acid hydrazide were once employed for treating leprosy caused by Mycobacterium leprae. 15 Pyridazine and fused pyridazine derivatives have long attracted the interest of Russian researchers as antituberculosis agents; antituberculosis compounds were found in the series of 3-pyridazinones 16 and pyridazino- [3,4-b]quinoxalines.…”