Synthesis, structure and biological activity of four new picolinohydrazonamide derivatives

Abstract

<jats:p>Four new picolinohydrazonamide derivatives, namely, 6-methyl-<jats:italic>N</jats:italic>′-(morpholine-4-carbonothioyl)picolinohydrazonamide, C<jats:sub>12</jats:sub>H<jats:sub>17</jats:sub>N<jats:sub>5</jats:sub>OS, 6-chloro-<jats:italic>N</jats:italic>′-(morpholine-4-carbonothioyl)picolinohydrazonamide methanol monosolvate, C<jats:sub>11</jats:sub>H<jats:sub>14</jats:sub>ClN<jats:sub>5</jats:sub>OS·CH<jats:sub>3</jats:sub>OH, 6-chloro-<jats:italic>N</jats:italic>′-(4-phenylpiperazine-1-carbonothioyl)picolinohydrazonamide, C<jats:sub>17</jats:sub>H<jats:sub>19</jats:sub>ClN<jats:sub>6</jats:sub>S, and 6-chloropicolinohydrazonamide, C<jats:sub>6</jats:sub>H<jats:sub>7</jats:sub>ClN<jats:sub>4</jats:sub>, 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, <jats:italic>i.e. P</jats:italic>2<jats:sub>1</jats:sub>/<jats:italic>c</jats:italic> (<jats:italic>P</jats:italic>2<jats:sub>1</jats:sub>/<jats:italic>n</jats:italic>), unlike the fourth structure which is chiral and has the space group <jats:italic>P</jats:italic>2<jats:sub>1</jats:sub>2<jats:sub>1</jats:sub>2<jats:sub>1</jats:sub>. 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.</jats:p>

Synthesis, structure, ADME and biological activity of three 2,6-disubstituted thiosemicarbazone derivatives

“…Structural elements of the INH molecule were exchanged in the following directions: changes within the functional group through the introduction of a thiosemicarbazone moiety instead of a hydrazide group, changes in the connection point of the functional group to the pyridine ring (from the C-4 to the C-2 position) and introduction of an additional substituent with different electronic properties to the C-4 position (Fig. 1) (Szczesio et al, 2020;Krause et al, 2020;Gobis et al, 2022;Ziembicka et al, 2023).…”

N′-Substituted 4-Phenylpicolinohydrazonamides with Thiosemicarbazone Moiety as New Potential Antitubercular Agents: Synthesis, Structure and Evaluation of Antimicrobial Activity

“…Previously, we described the synthesis and antimicrobial properties of the cycloalkylamine-1-thiosemicarbazone derivatives of picolinohydrazonamide DMK-15 and ACSc-5 (Figure 1) [11,12]. The first one, with two rings of secondary cyclic amines, pyrrolidine and morpholine, showed tuberculostatic activity towards M. tuberculosis at the MIC (minimal inhibition concentration) level of 0.4 µg/mL with low cytotoxicity against the human dermal fibroblast line HDF, with IC50 (half-maximal inhibitory concentration) of 36.18 µg/mL.…”