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

Abstract

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.

Novel Thiosemicarbazone Derivatives from Furan-2-Carbaldehyde: Synthesis, Characterization, Crystal Structures, and Antibacterial, Antifungal, Antioxidant, and Antitumor Activities

“…In the crystal structure of 6, the phenyl group is not coplanar with the furan ring, as evidenced by the dihedral angle of 2.56 (8) °and by the torsion angles C1-C6-C7-O1: 25.1(2) and C1-C6-C7-C8: −148.4(2) °. However, for 7 and 8 the presence of the fuoro and methoxy substituent groups attached to the C2′ and C4′ carbons of the phenyl fragment cause a certain coplanarity with the furan ring, being demonstrated by the dihedral angles of 13.53 (9) °in 7 and 3.47 (6) °in 8 (Table S1, supplementary material) as well as by the torsion angles C1-C6-C7-O1: 172.6(1) and C5-C6-C7-O1: 10.6(2) °for 7, and C1-C6-C8-O2: −3.6(2) and C5-C6-C8-O2: 177.2(1) °for 8. In all studied crystal structures, the furan ring is coplanar with the thiosemicarbazone fragment within a deviation of ±11 °.…”

“…Tese compounds which contain N and S atoms usually act as bidentate or multidentate chelating ligands and can coordinate to transition metal ions through the sulfur and hydrazine nitrogen atoms [1]. Extensive investigations conducted by researchers have demonstrated that metal complexes with some thiosemicarbazone derivatives present a wide range of biological applications, such as antibacterial [2,3], antifungal [1,4], antiparasitic [5], antitubercular [6,7], antiviral [8,9], antioxidant [10,11], and antitumoral activities [12][13][14].…”