RP-HPLC analysis and in vitro identification of antimycobacterial activity of novel thiosemicarbazides and 1,2,4-triazole derivatives.

It has been widely recognized that chromatography can be applied to derive parameters useful for anticipation of the pharmacological properties of xenobiotics. The purpose of this study was to evaluate the use of C18 stationary phase in chromatographic experiments as to assess antimycobacterial activity of series of novel thiosemicarbazides and their cyclization products: 1,2,4-triazole derivatives. Chromatographically determined lipophilicity descriptors log k(w), S and φ0 and computer generated molecular descriptors were obtained for 32 compounds and Rifampicin as a representative anti-tuberculosis drug. As experimental parameters were not significantly related to the calculated values, the data were analyzed by the principal component analysis PCA allowing for the extraction of "dipole moment" and "energy due to solvation" as the most powerful parameters from large set of diverse data. The approach ranked the examined analytes as active and inactive against Mycobacterium strains. More significant clustering of examined compounds was achieved by construction of 3D graph relating computational (dipole moment, energy due to solvation) and experimental log k(w) (MeOH) descriptors. It was proved that lack of substituent in the C5 position in the triazole ring appears to be characteristic for active derivatives. Provided conclusions can be taken into account in planning further synthesis of new derivatives with antimycobacterial activity.