Marcelle de Lima Ferreira

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.

Synthesis and Biological Aspects of Mycolic Acids: An Important Target Against Mycobacterium tuberculosis

Mycolic acids are an important class of compounds, basically found in the cell walls of a group of bacteria known as mycolata taxon, exemplified by the most famous bacteria of this group, the Mycobacterium tuberculosis (M. tb.), the agent responsible for the disease known as tuberculosis (TB). Mycolic acids are important for the survival of M. tb. For example, they are able to help fight against hydrophobic drugs and dehydration, and also allow this bacterium to be more effective in the hosts immune system by growing inside macrophages. Due to the importance of the mycolic acids for maintenance of the integrity of the mycobacterial cell wall, these compounds become attractive cellular targets for the development of novel drugs against TB. In this context, the aim of this article is to highlight the importance of mycolic acids in drug discovery.

Structures of arylaldehyde 7-chloroquinoline-4-hydrazones: supramolecular arrangements derived from N-H···N, C - H ...X (X = N, O, or π) and π···π interactions

Abstract The molecules of the 7-chloroquinoline-4-hydrazones of the variously substituted benzaldehydes, 5, of general formula C16H11ClN3X with X = H, o-F, m-F or m-MeO corresponding to compounds (5: X = H), (5: X = o-F), (5: X = m-F) and (5: X = m-MeO), respectively, are formally rather similar. Compounds (5: X = H) and (5: X = o-F) are isostructural but otherwise the molecular packing and intermolecular interactions show unexpectedly wide variation throughout the series. In all 5 hydrogen-bonds link the essentially planar molecules edge to edge to form chains. Combination of intermolecular hydrogen-bonds and π···π interactions creates three-dimensional connectivity in (5: X = H), (5: X = o-F) and, utilising the methoxy oxygen atom as acceptor for a C—H···O hydrogen-bond, (5: X = m-MeO). Significant connectivity is no more than two-dimensional in layers of molecules in (5: X = m-F).

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 μg/mL), which can be compared to that of the first-line drugs ethambutol (3.12 μg/mL) and rifampicin (2.0 μg/ml). These results can be considered an important starting point for the rational design of new leads for anti-TB compounds.

Synthesis and Biological Evaluation of N,N′-di(thiopheneacetyl)diamines Series as Antitubercular Agents

The series of new N,N′-di(thiopheneacetyl)diamines derivatives, 8–17, were synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis(TB), and the activity expressed as the minimum inhibitory concentration (MIC) in μ g/mL. Compound 13 was the only one determined to be active and exhibited a MIC 50 μg/mL, indicating that the alkyl chain-length of the diamines is critical for biological activity. This class of compound has not been evaluated before, and it could be a good starting point to find new lead compounds in the fight against multi-drug resistant TB.

4-[(E)-2-(2-Chloro­benzyl­idene)hydrazin-1-yl]quinolin-1-ium chloride dihydrate

In the title hydrated salt, C16H12Cl2N3 +·Cl−·H2O, there is a small twist in the cation as seen in the torsion angle linking the benzene ring to the rest of the molecule [171.96 (17)°]. In the crystal, the quinolinium H atom forms a hydrogen bond to the lattice water molecule, which also forms hydrogen bonds to two Cl− anions. Each Cl− ion also accepts a hydrogen bond from the hydrazine H atom. The three-dimensional architecture is also stabilized by π–π interactions between centrosymmetrically related quinoline residues [centroid–centroid distance = 3.5574 (11) Å].

7-Chloro-4-[(E)-2-(3,4,5-trimeth-oxy-benzyl-idene)hydrazin-1-yl]quinoline.

In the title compound, C19H18ClN3O3, the r.m.s. deviation through the 23 non-H and non-methoxy atoms is 0.088 Å, indicating a planar molecule with the exception of the methoxy groups. One methoxy group, surrounded on either side by the other methoxy groups, is almost normal to the benzene ring to which it is connected [C—O—Car—Car torsion angle = 81.64 (15)°]. In the crystal, N—H⋯O, C—H⋯O and π–π interactions [between quinoline residues; centroid–centroid distance = 3.4375 (8) Å] link molecules into a three-dimensional architecture.

N-(4-Bromophenyl)pyrazine-2-carboxamide

The molecule of the title compound, C11H8BrN3O, is close to planar (r.m.s. deviation of all 16 non-H atoms = 0.103 Å), a conformation stabilized by an intramolecular N—H⋯N hydrogen bond, which generates an S(5) ring. In the crystal structure, supramolecular chains mediated by C—H⋯O contacts (along a) are linked into a double layer via N⋯Br halogen bonds [3.207 (5) Å] and C—Br⋯π interactions [Br⋯ring centroid(pyrazine) = 3.446 (3) Å]. The layers stack along the b axis via weak π–π interactions [ring centroid(pyrazine)⋯ring centroid(benzene) distance = 3.803 (4) Å].

In vivo and in vitro antimalarial effect and toxicological evaluation of the chloroquine analogue PQUI08001/06

Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant and -sensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.