Synthesis and antitubercular activity of heteroaromatic isonicotinoyl and 7-chloro-4-quinolinyl hydrazone derivatives.

Two series of N'-(E)-heteroaromatic-isonicotinohydrazide derivatives (3a-f and 4a-b) and 1-(7-chloroquinolin-4-yl)-2-[(heteroaromatic)methylene]hydrazone derivatives (5a-f and 6a-b) have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Several compounds were noncytotoxic and exhibited significant minimum inhibitory concentration (MIC) activity (3.12, 2.50, 1.25, or 0.60 microg/mL), which can be compared to that of the first-line drugs ethambutol (3.12 microg/mL) and rifampicin (2.0 microg/ml). These results can be considered an important starting point for the rational design of new leads for anti-TB compounds.

Synthesis and antitubercular activity of 7-chloro-4-quinolinylhydrazones derivatives.

A series of twenty-one 7-chloro-4-quinolinylhydrazones (3a-u) have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H(37)Rv. The compounds 3f, 3i and 3o were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity (2.5 microg/mL), which can be compared with that of the first line drugs, ethambutol (3.12 microg/mL) and rifampicin (2.0 microg/mL). These results can be considered an important start point for the rational design of new leads for anti-TB compounds.

Synthesis and antimycobacterial activity of N'-[(E)-(monosubstituted-benzylidene)]-2-pyrazinecarbohydrazide derivatives.

The present article describes a series of twenty-six N'-[(E)-(monosubstituted-benzylidene)]-2-pyrazinecarbohydrazide (4-29), which were synthesized and evaluated for their cell viabilities in non infected and infected macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). Afterwards, the non-cytotoxic compounds (4, 6, 8, 15, 21, 23, 24, 27 and 28) were assessed against Mycobacterium tuberculosis ATCC 27294 using the micro plate Alamar Blue assay (MABA) and the activity expressed as the minimum inhibitory concentration (MIC) in microg/mL. The compounds 6, 23, 27 and 28 exhibited a significant activity (50-100 microg/mL) when compared with first line drugs such as pyrazinamide and were not cytotoxic in their respective MIC values.

Synthesis and antitubercular activity of novel Schiff bases derived from d-mannitol.

Six Schiff base derivatives of d-mannitol, 1,6-dideoxy-1,6-bis-{[(E)-arylmethylidene]amino}-d-mannitol (6: aryl=XC(6)H(4): X=o-, m- and p- Cl or NO(2)), have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H(37)Rv using the Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC) in microg/mL. All three nitro derivatives exhibit significant activities: activities of (6d: X=o-NO(2)), (6e: X=m-NO(2)) and (6f: X=p-NO(2)) are 12.5, 25.0 and 25.0microg/mL, respectively. When compared with first line drugs, such as ethambutol, they can be considered as a good starting point to develop new lead compounds for the treatment of multidrug-resistant tuberculosis. Characterization of the new compounds 6 is generally achieved spectroscopically. The structure of compound 3 has been confirmed by X-ray crystallography.

Patterns of hydrogen bonding in mono- and di-substituted N-arylpyrazinecarboxamides.

The molecular and supramolecular structures of 18 N-arylpyrazinecarboxamides, Ar NHCO(C(4)H(3)N(2)), have been determined, including the stoichiometric monohydrate of N-(3-methoxyphenyl)pyrazinecarboxamide, and two polymorphs of N-(4-fluorophenyl)pyrazinecarboxamide having Z' values of 1 and 4, respectively. The aryl groups were selected to include the geometric isomers for a compact range of substituents, namely methyl, trifluoromethyl, fluoro, chloro, methoxy and nitro groups, which exhibit markedly varied electronic properties and markedly varied behaviour as hydrogen-bond donors and acceptors. However, not all isomers in each group could be structurally investigated. A small number of derivatives containing disubstituted aryl groups have also been included in this study. The crystal structures of the solvent-free carboxamides reported here exhibit a wide range of direction-specific intermolecular forces, including N-H...N, N-H...O, C-H...N and C-H...O hydrogen bonds, and pi...pi stacking interactions, while the structure of N-(3-methoxyphenyl)pyrazinecarboxamide monohydrate also contains O-H...N and O-H...O hydrogen bonds. The resulting supramolecular structures can be zero-, one- or two-dimensional, although no three-dimensional supramolecular aggregation has been observed. In the finite, zero-dimensional structures, pairs of molecules are linked by hydrogen bonds to form cyclic centrosymmetric dimers. The one-dimensional structures include chains formed by the pi-stacking of otherwise isolated molecules, simple chains generated by either C-H...O or C-H...N hydrogen bonds, and hydrogen-bonded chains of rings. The two-dimensional structures include examples of both pi-stacked hydrogen-bonded chains and hydrogen-bonded sheets.

pi-Stacked hydrogen-bonded chains of rings in 2,4-difluorobenzaldehyde isonicotinoylhydrazone and hydrogen-bonded sheets in 2,3-dichlorobenzaldehyde isonicotinoylhydrazone.

The difluorinated ring in 2,4-difluorobenzaldehyde isonicotinoylhydrazone, C13H9F2N3O, (I), is disordered over two sets of sites with unequal occupancy. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds into chains of rings, which are linked into sheets by a single pi-pi stacking interaction. In 2,3-dichlorobenzaldehyde isonicotinoylhydrazone, C13H9Cl2N3O, (II), the molecules are linked by a combination of N-H...N, C-H...N and C-H...O hydrogen bonds into sheets of R(4)(4)(14) and R(4)(4)(26) rings.