RESUMO
Three new 4-phenylpicolin derivatives with a thiosemicarbazone structure were synthesized and evaluated for tuberculostatic activity. The compounds were obtained by the condensation of methyl 4-phenylpicolonimidate with the corresponding cycloalkylamino-1-carbothiohydrazides. The 1H NMR temperature spectra obtained showed proton lability at the nitrogen atom N2, and X-ray crystallography confirmed the zwitterionic structure of all products. ADME calculations indicate that the compounds can be tested as future drugs. All compounds were absorbed in the gastrointestinal tract. All compounds also showed very good tuberculostatic activity (MIC 3.1-12.5 µg/mL). Derivative 1b showed the best selectivity for M. tuberculosis compared to the other pathogenic species tested. The study has allowed the emergence of imine derivative 1b as a good structure for further optimization in the search for antitubercular drugs.
RESUMO
Four new picolinohydrazonamide derivatives, namely, 6-methyl-N'-(morpholine-4-carbonothioyl)picolinohydrazonamide, C12H17N5OS, 6-chloro-N'-(morpholine-4-carbonothioyl)picolinohydrazonamide methanol monosolvate, C11H14ClN5OS·CH3OH, 6-chloro-N'-(4-phenylpiperazine-1-carbonothioyl)picolinohydrazonamide, C17H19ClN6S, and 6-chloropicolinohydrazonamide, C6H7ClN4, have been synthesized and characterized by NMR spectroscopy and single-crystal low-temperature X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The first three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules in the structure. They also adopt the same symmetry, i.e. P21/c (P21/n), unlike the fourth structure which is chiral and has the space group P212121. For all the studied cases, intermolecular N-H...O and N-H...N hydrogen bonds play an essential role in the formation of the structures.
