Synthesis, anti-tuberculosis activity, and 3D-QSAR study of ring-substituted-2/4-quinolinecarbaldehyde derivatives

We have previously identified ring-substituted quinolines as a new structural class of anti-tuberculosis agents. In our ongoing efforts at structural optimization of this class, four series of ring-substituted-2/4-quinolinecarbaldehyde derivatives were synthesized. All twenty-four compounds were synthesized using short and convenient one to two high yielding steps. The newly synthesized compounds were tested in vitro against drug-sensitive Mycobacterium tuberculosis H37Hv strain. Several derivatives were found to be promising inhibitors of M. tuberculosis. For example, derivatives 4a–c (Series 2), 7a–d (Series 3), and 8a–b (Series 4) displayed >90% inhibition at 6.25 μg/mL in the primary assay. The most active compounds, N-(2-fluorophenyl)-N′-quinolin-2-ylmethylene-hydrazine (4a), N-(2-adamantan-1-yl-quinolin-4-ylmethylene)-N′-(4-fluorophenyl)hydrazine (7c), and N-(2-cyclohexyl-quinolin-4-ylmethylene)-N′-(2-fluorophenyl)hydrazine (8a), exhibited 99% inhibition at the lowest tested concentration of 3.125 μg/mL against drug-sensitive M. tuberculosis H37Rv strain. The similarity index based on steric and electrostatic features of the molecules was used, in conjunction with principal component analysis and linear discriminant analysis, successively to classify the molecules based on their activity into two classes. This classification method gives us confidence in predicting the activity class of any new unsynthesized molecule belonging to these series

Synthesis and structural studies of novel 1,3,4-oxadiazolophanes

397-400The title compounds have been prepared in moderate yields from compound 2a/2b as starting unit, which are obtained, in good yields by one-step process in high purity. Interesting results have been obtained when the cyclisation products were studied for structural analysis. The title compounds are also studied for their use as PTC agents.