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Two new 2-(pyridin-2-yl)-1H-benzimidazole derivatives, namely, 2-(4-phenoxypyridin-2-yl)-1H-benzimidazole, C 18 H 13 N 3 O, and 2-[4-(4-fluorophenoxy)pyridin-2-yl]-1H-benzimidazole, C 18 H 12 FN 3 O, were synthesized and characterized by NMR spectroscopy. Crystal structure, biological activity and ADME analyses were performed for these two new compounds and a third compound, namely, 5,6-dimethyl-2-[4-(4-phenylpiperazin-1-yl)pyridin-2-yl]-1H-benzimidazole methanol monosolvate, C 24 H 25 N 5 ·CH 3 OH, the synthesis of which had been described previously. All three compounds have a similar chain hydrogen-bonding pattern. One of them (the fluorophenoxy derivative) showed good antimicrobial activity against Gram-positive bacteria. The ADME analysis indicates that the compounds could be good drug candidates.

Three new 2,6-disubstituted thiosemicarbazone derivatives of pyridine, namely, 2-{amino[6-(pyrrolidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C 13 H 20 N 6 S, 2-{amino[6-(piperidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C 14 H 22 N 6 S, and 2-[amino(6-phenoxypyridin-2-yl)methylidene]-N,N-dimethylhydrazine-1-carbothioamide monohydrate, C 15 H 17 N 5 OS·H 2 O, have been synthesized and characterized by NMR spectroscopy and low-temperature single-crystal X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The ability of the tested compounds to inhibit bacterial growth was comparable to vancomycin as a reference drug. Compared to isoniazid (MIC 0.125 and 8 µg ml -1 ), the compounds showed the ability to inhibit the growth of Mycobacterium tuberculosis to a moderate degree for the standard strain and at the same level or higher (MIC 4-8 µg ml -1 ) for the resistant strain. All three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules.

Four new picolinohydrazonamide derivatives, namely, 6-methyl-N'-(morpholine-4-carbonothioyl)picolinohydrazonamide, C 12 H 17 N 5 OS, 6-chloro-N'-(morpholine-4-carbonothioyl)picolinohydrazonamide methanol monosolvate, C 11 H 14 ClN 5 OS·CH 3 OH, 6-chloro-N'-(4-phenylpiperazine-1-carbonothioyl)picolinohydrazonamide, C 17 H 19 ClN 6 S, and 6-chloropicolinohydrazonamide, C 6 H 7 ClN 4 , 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. P2 1 /c (P2 1 /n), unlike the fourth structure which is chiral and has the space group P2 1 2 1 2 1 . 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.

Tuberculosis still remains a very important problem, especially its multidrug resistant varieties (MDR-TB). Among the potential tuberculostatics, there are two benzimidazole derivatives, namely 5,6-dimethyl-2-phenylethylbenzo[d]imidazole (1) and (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazole (2) which showed significant tuberculostatic activities, better than those of Pyrazinamide and Isoniazyd. Also, the cytotoxicity of 1 appeared promising. The compounds were studied (with the use of X-ray diffraction) in the form of the hemihydrate of 1, C 17 H 18 N 2 ·0.5H 2 O (1a), the methanol hemisolvate of 2, C 17 H 16 N 2 ·0.5CH 3 OH (2a), and the acid oxalate salt of 2, namely (E)-5,6-dimethyl-2-styryl-1H-benzo[d]imidazolium hydrogen oxalate, C 17 H 17 N 2 + ·C 2 HO 4 - (2b). All three structures reveal a similar extended conformation, despite the flexible linker between the two aromatic systems and the different types of strong intermolecular hydrogen bonds. The molecules of 2a are practically planar due to the double bond in the linker, which enables conjugation along the whole molecule, while the molecules of 1a exhibit the possibility of parallel orientations of their aromatic systems, despite the aliphatic (ethyl) linker.

The search for new tuberculostatics is an important issue due to the increasing resistance of Mycobacterium tuberculosis to existing agents and the resulting spread of the pathogen. Heteroaryldithiocarbazic acid derivatives have shown potential tuberculostatic activity and investigations of the structural aspects of these compounds are thus of interest. Three new examples have been synthesized. The structure of methyl 2-[amino(pyridin-3-yl)methylidene]hydrazinecarbodithioate, C 8 H 10 N 4 S 2 , at 293 K has monoclinic (P2 1 /n) symmetry. It is of interest with respect to antibacterial properties. The structure displays N-H...N and N-H...S hydrogen bonding. The structure of N'-(pyrrolidine-1-carbonothioyl)picolinohydrazonamide, C 11 H 15 N 5 S, at 100 K has monoclinic (P2 1 /n) symmetry and is also of interest with respect to antibacterial properties. The structure displays N-H...S hydrogen bonding. The structure of (Z)-methyl 2-[amino(pyridin-2-yl)methylidene]-1-methylhydrazinecarbodithioate, C 9 H 13 N 4 S 2 , has triclinic (P-1) symmetry. The structure displays N-H...S hydrogen bonding.

The search for new tuberculostatics is important considering the occurrence of drug-resistant strains of Mycobacterium tuberculosis. Three polymorphs of N'-(1,3-dithiolan-2-ylidene)-4-nitrobenzohydrazide (a potentially tuberculostatic agent), C 10 H 9 N 3 O 3 S 2 , denoted (I1), (I2) and (I3), and the monohydrate of this compound, C 10 H 9 N 3 O 3 S 2 ·H 2 O, (I4), have been characterized by single-crystal X-ray diffraction. The conformations of the molecules in all these structures are very similar. Structures (I1), (I2) and (I3) provide an example of packing polymorphism resulting from different intermolecular interactions.

Searches for new tuberculostatic agents are important considering the occurrence of drug-resistant strains of Mycobacterium tuberculosis. The structures of three new potentially tuberculostatic compounds, namely isopropyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, C 12 H 16 N 2 O 2 S 2 , (Z)-benzyl methyl (2-hydroxybenzoyl)carbonohydrazonodithioate, C 16 H 16 N 2 O 2 S 2 , and dibenzyl (2-hydroxybenzoyl)carbonohydrazonodithioate propan-2-ol monosolvate, C 22 H 20 N 2 O 2 S 2 ·C 3 H 8 O, were determined by X-ray diffraction. The mutual orientation of the three main fragments of the compounds, namely an aromatic ring, a dithioester group and a hydrazide group, can influence the biological activity of the compounds. In all three of the structures studied, the C(=O)NH group is in the anti conformation. In addition, the presence of the hydroxy group in the ortho position of the aromatic ring in all three structures leads to the formation of an intramolecular hydrogen bond stabilizing the planarity of the molecules.

The emergence of drug-resistant strains of Mycobacterium tuberculosis has intensified efforts to identify new lead tuberculostatics. Our earlier studies concluded that the planarity of a molecule correlates well with its tuberculostatic activity. According to our hypothesis, only derivatives whose molecules are capable of adopting a planar conformation may show tuberculostatic activity. The structures of three new potentially tuberculostatic compounds, namely N'-[bis(methylsulfanyl)methylidene]-N-methyl-4-nitrobenzohydrazide (denoted G1), C11H13N3O3S2, N'-[bis(benzylsulfanyl)methylidene]-N-methyl-4-nitrobenzohydrazide (denoted G2), C23H21N3O3S2, and N'-[(benzylsulfanyl)(methylsulfanyl)methylidene]-4-nitrobenzohydrazide (denoted G3), C16H15N3O3S2, were determined by X-ray diffraction. The significant distortion from planarity caused by the methyl substituent at the N atom of the hydrazide group or the NO2 substituent in the aromatic ring leads to the loss of tuberculostatic activity for G1, G2 and G4 {systematic name: N'-[bis(methylsulfanyl)methylidene]-2-nitrobenzohydrazide}. A similar effect is observed when there are large substituents at the S atoms (G2 and G3).